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Objectives: To classify clinical diseases of the subjects with abnormal indices of peripheral neuropathy identified in field studies of sheep farmers and dippers exposed to organophosphate pesticides. To explore what neuropsychological profiles, if any, may be associated with neurophysiological damage in these subjects., Methods: A case-control study (79 subjects) nested within the cross sectional study (685 subjects) of sheep farmers from the field study. Three groups with no, possible, and probable or definite neuropathy according to field studies were recruited. Investigations comprised symptoms of neuropathy, neurologial signs, motor and sensory nerve conduction, electromyography, quantitative sensory testing, and neuropsychological tests., Results: The incidence of clinical neuropathy increased from 7% in the no neuropathy group to 52% in the probable or definite neuropathy group based on nerve conduction measurements or presence of neurological signs. Sensory abnormalities were found more often than motor deficits. Small diameter nerve fibres were also affected more than large fibres., Conclusions: The neuropathy is predominantly sensory and is characteristic of distal, chronic neuropathy with no acute features. Small fibre populations are affected more than large fibre populations. Increasing severity of neuropathy was associated with anxiety and depression as measured in the neuropsychological tests.

We report a patient with sympathetically maintained pain following a mild limb injury. Only emotional sudomotor failure was found in the painful limb. Thermoregulatory vasomotor function was intact. However, the patient had other target-specific sympathetic lesions, including thermoregulatory vasomotor failure in a different limb, not associated with pain. We hypothesize that the sympathetic failure preceded the symptoms and that the mild injury may have provoked collateral sprouting of emotional sudomotor fibres, coupling them with somatic sensory fibres to cause continuous pain.

We report a symptomatic failure of the baroreceptor blood pressure (BP) buffering mechanism in a woman with familial aniridia. Her baseline BP oscillated at 0.1 Hz, the frequency of Mayer waves, with increased amplitude on standing without orthostatic hypotension. Although sudomotor function was normal, cutaneous thermoregulatory function and BP response to Valsalva's maneuver were abnormal. The defective BP buffer mechanism suggests Mayer waves could be a sympathetic mediated cardiovascular resonance. Baroreceptor cardioinhibition was intact. We presume that the lesion is in the rostral aspect of the dorsal medulla oblongata.

We describe a man with a thoracic disk prolapse whose major manifestation for 10 years was Lhermitte's symptom precipitated by a rotatory movement of the thoracic spine during during the golf swing.

We have recently reported abnormalities of single fibre EMG in patients with multiple sclerosis. The present study applies quantitative electrophysiological techniques to the same group of patients. The number of motor units in the extensor digitorum brevis muscle was measured and their characteristics recorded. Also the shortest distal motor latency and fastest motor conduction velocities were estimated. Abnormalities suggesting a patchy denervating/reinnervating process due to pathology in the intramuscular nerve network or at the endplate were found in a number of patients. There was a good correlation between patients with abnormal motor unit potentials and those with abnormal single fibre EMG "jitter".

Results of comprehensive serial neurophysiological tests from onset to full recovery in 3 patients with the Miller Fisher syndrome (acute ophthalmoplegia, ataxia and areflexia) are presented. These included EMG and nerve conduction, late response (H and F wave) and direct facial motor and blink reflex studies, computerized motor unit number estimation, automated quantitative sensory threshold measurements, quantitative pupillometric and pupillopharmacological studies and multimodality evoked potential (VEP, SEP and BAEP) and EEG recordings. The results provided unequivocal evidence of peripheral nerve dysfunction. Improvement of the peripheral neurophysiological parameters accompanied or followed clinical recovery in all 3 patients. No abnormality in the CNS pathways investigated by these tests was found. The findings support the conclusion that this syndrome is to be included within the spectrum of acute inflammatory polyneuropathy. The value of serial measurements in detecting milder peripheral nerve lesions is emphasized.

Thirty-two patients with motor neurone disease were investigated using quantitative electrophysiological techniques. Estimates of the number of surviving motor units in the extensor digitorum brevis muscle and measurements of the electrophysiological parameters of these units are present along with the values for motor nerve conduction velocities. The results indicate that reinnervation in motor neurone disease is sufficient to compensate completely for the loss of up to 50% of the motor neurone pool supplying the muscle. The capacity for reinnervation is greater than we have found in a number of neuropathies but the efficiency of reinnervation decreases as the number of surviving motor units falls. Reinnervation appears to cease when 5% or less of the motor units remain viable. There is no electrophysiological evidence of a preferential loss of fast conducting axons, of pathological slowing of conduction nor of a dying-back process affecting the motor axon. Comparison of the electrophysiological parameters in progressive muscular atrophy and amyotrophic lateral sclerosis shows no significant differences. The underlying pathophysiological mechanisms are discussed in terms of the results.

A new method, incorporating on-line computer analysis, is described for the estimation of the numbers of motor units in human muscle. The results obtained in the extensor digitorum brevis muscle in normal subjects and patients with myasthenia gravis are presented. These indicate that the numbers of motor units in that muscle in patients with myasthenia gravis are within the normal range, in contrast with the reduction in numbers reported by other workers using a different technique. Evidence is presented to suggest that the discrepancy in these results is due to increased sensitivity and discrimination of the computerized method. Several hypotheses on the aetiology of a number of neuromuscular diseases, based on the results of the other method, may require reevaluation.

A series of complementary neurophysiological investigations was carried out on 24 patients with myotonic dystrophy to determine the extent of nervous system involvement. Conventional electromyography and nerve conduction studies, computerized motor unit number estimation and motor unit potential analysis, vibration threshold studies and a recently introduced technique for heat and cold threshold estimations were undertaken in all patients. The results provide unequivocal evidence of widespread nervous system dysfunction. In many patients there is significant involvement of peripheral large diameter motor and sensory fibres and of small diameter sensory fibres either peripherally and/or centrally. In the light of these results and others reviewed in the literature, the concept of myotonic dystrophy as a pure myopathy can no longer be sustained.

Clinical tests of thermal sensation are poorly quantified and not strictly modality specific. Previous automated thermal testing systems have had limited usefulness with high intra-and inter-individual variability. This paper describes an automated thermal system (Glasgow system) which is an extensive modification of previous techniques to answer these criticisms. It comprises a microprocessor-driven Peltier element and utilises the forced choice method of psychophysical analysis to determine the thresholds to thermal stimulation. In a control group of 106 healthy subjects the mean heat threshold for the wrist was found to be 0.23 degree C (SD = 0.06 degree C) and the mean cold threshold 0.15 degree C (SD = 0.05 degree C). Repeated determinations showed a maximum of 5% intra-individual variation in comparison to previously reported values of up to 150%.

The numbers of functioning motor units and the parameters of the electrically evoked motor unit potentials in the extensor digitorum brevis muscles of 30 patients on chronic haemodialysis for renal failure were obtained using recently introduced quantitative electrophysiological techniques. Measurements of the distal motor latencies and motor nerve conduction velocities in the lateral popliteal nerves of the same patients are also presented. The results support the presence of a "dying back" type of neuropathy in uraemia, with a preferential involvement of the fastest conducting motor axons. Collateral reinnervation and compensatory increase in size of surviving motor units is relatively impaired in uraemic neuropathy in comparison with a similar study on diabetic neuropathy. The significance of paranodal and segmental demyelination in producing abnormalities of conduction velocity in these neuropathies is discussed.

Thirty-one chronic alcoholic patients were investigated using quantitative electrophysiological techniques. Estimates of the numbers of functioning motor units in the extensor digitorum brevis muscles and measurements of the parameters of the potentials of these units are presented along with the values for motor nerve conduction velocities in the innervating lateral popliteal nerves. Motor conduction velocities and sensory nerve action potential amplitudes were also measured in the ulnar nerves. The results and their inter-relationships lead us to conclude that the slowing of motor nerve conduction and reduction in sensory nerve action potential amplitudes in alcoholic neuropathy are a consequence of axon loss. We found no evidence of pathological slowing of conduction in surviving axons. Reinnervation by functioning motor axons is poor compared to a number of other neuropathic conditions. In our patients there was no evidence of preferential involvement of sensory axons. The results support a predominant axonal dysfunction in alcoholic neuropathy.

Recent histological and electrophysiological reports have given evidence for peripheral nervous system (PNS) involvement in multiple sclerosis. We have applied the single fibre electromyography (SFEMG) technique to 15 patients with multiple sclerosis. Six patients had clearly abnormal jitter and two of these had previously undiagnosed coexistent peripheral neuropathy. A further five patients had borderline abnormalities of SFEMG. The mean jitter for each patient was abnormal in 10 patients. This was clear evidence for PNS involvement in this disease. Theoretically, the site of the abnormality could be in the terminal nerve network or at the neuromuscular junction, but this technique cannot distinguish between these sites.

Electrophysiological studies were undertaken on 29 patients with Alzheimer's Disease. A reduction in the number of functioning motor units was found in the extensor digitorum brevis muscle. The electrophysiological parameters of the motor unit potentials were increased compared to control values. Four of seven muscle biopsies showed abnormalities ranging from mild to severe. The results suggest dysfunction in the lower motor neurone in this disease.

In six healthy subjects cortical potentials were evoked by rapidly changing heating or cooling stimuli to the hand. Recordings were made from the contralateral scalp area overlying the sensori-motor cortex, referred to a frontal reference. The potential averaged from 25 stimuli comprised a large positive wave with a mean amplitude of 9.2, SD 1.1 microV for heat and 8.8 SD 1.2 micro V for cold stimulation. The heat evoked potentials had longer peak latencies (range: 280-350 ms) than those elicited by cold stimuli (range: 178-200 ms). A lower amplitude positive wave of a longer latency was also recorded to both modes of stimulation over the corresponding ipsilateral cortex. Cortical thermal evoked potentials were absent in two patients, one with severe selective small fibre neuropathy and the other with syringomyelia, both of whom had high thermal thresholds demonstrated by the technique of Jamal et al. Cerebral potentials evoked by thermal stimuli may represent an alternative approach to the investigation of the central projections of the human small fibre system with both clinical and research potential.

We have applied our technique for the measurement of thermal thresholds to 25 patients referred with symptoms and signs of small fiber peripheral neuropathy in whom conventional electrophysiological indices were individually within the range of normal values for our laboratory. Vibration threshold determinations were also within normal range. Significant abnormalities of thermal thresholds were noted in all patients. The results indicate that the technique provides an accurate, easily performed and reproducible index of function in small A delta and C groups of nerve fibers.

Routine clinical electrophysiological techniques assess function in the large diameter, motor and sensory nerve fibres, but not in the smaller diameter fibres subserving pain, thermal sensation and autonomic function. The instrument we describe measures thermal sensation thresholds to both cooling and warming thus providing an index of function in the small diameter thinly myelinated A delta fibres and unmyelinated C fibers respectively. A commercial version, the Thermal Threshold Tester (TRIPLET) provides a portable instrument for routine clinical use. It has a particularly important role in the sequential and quantitative monitoring of small nerve fibre function as for example in diabetic neuropathy. It can also be applied to the study of small nerve fibre function in persons exposed to potentially neurotoxic substances either as medication or in industry.

Thermal thresholds were determined in 40 patients with motor neuron disease and in 40 age- and sex-matched healthy subjects. The thermal thresholds were estimated on the skin of wrist and ankle using an automated microprocessor controlled system and the "two alternative forced-choice method" of psycholphysical analysis. Abnormalities of thermal thresholds (greater than or equal to 99th percentile) were seen in 80% of the motor neuron disease patients. The results are in agreement with reports of sensory pathway involvement in the literature. Thermal threshold abnormalities are common in motor neuron disease and indicate the involvement of the small fibre afferent pathways.

Thermal thresholds were determined by a new technique, at wrists and ankles in 143 patients with peripheral neuropathies of diverse aetiologies. Ninety-nine percent of patients (141/143) had abnormalities of one or both thresholds. In only two patients with mild/early Friedreich's ataxia were thermal thresholds normal. Electromyography was performed and fastest motor nerve conduction velocities and sensory nerve action potential parameters were measured in all the patients using conventional techniques in ulnar, median and sural nerves. Eighty-nine percent of patients (127/143) had one or more abnormalities on these electrophysiological studies. However, 39 of 40 patients with completely normal sensory nerve studies had an abnormality of one or more thermal thresholds. Eighty-six percent of 48 patients with normal sural nerve studies had abnormal thermal thresholds at the ankle. Sixty percent of 70 patients with normal sensory median and ulnar nerve studies had abnormal wrist thermal thresholds. This improved technique for the determination of thermal thresholds reveals that disturbances of thermal sensibility are present in the majority of peripheral neuropathies irrespective of aetiology. In some patients disturbances of thermal thresholds antedate the appearance of abnormalities on conventional electrophysiological investigation. The findings suggest that this technique has considerable usefulness in the detection of small nerve fibre dysfunction in the context of generalised neuropathy.

Single motor unit potentials recorded from surface electrodes over the extensor digitorum brevis muscle and evoked by stimulation of the anterior tibial nerve at the ankle were obtained by a computer subtraction method. Their latencies, durations, amplitudes, and areas were measured in control subjects and patients with Duchenne, limb-girdle, facioscapulohumeral, and myotonic muscular dystrophy. Lateral popliteal motor nerve conduction velocities were also recorded. In the muscular dystrophies there was a significant increase in both the latencies and durations of motor unit potentials, the latter in notable contrast with the findings of conventional needle electromyography. Fastest motor conduction velocities were significantly reduced in the limb-girdle, facioscapulohumeral, and myotonic muscular dystrophy patients, while the shortest distal motor latencies were significantly prolonged in these patients and those with Duchenne muscular dystrophy. The results support the presence of a definitive neurogenic influence in the muscular dystrophies.

Abnormal calcium transport may be implicated in the membrane defect in myotonic dystrophy. A single blind crossover trial of placebo (t.i.d.), nifedipine 10 mg (t.i.d.) and nifedipine 20 mg (t.i.d.), was performed in 10 patients with myotonic dystrophy. The severity of myotonia was assessed by measuring finger extension time after maximum voluntary finger flexion. A significant improvement in myotonia, after nifedipine, was recorded by this technique and supported by a subjective improvement in 50% of patients and clinical improvement of greater than 20% in five patients. Initial grip strength and muscle fatiguability measured by grip strength ergometry were not significantly altered.

The results of the application of a computerized method for the estimation of motor unit numbers in the human extensor digitorum brevis are presented. In patients with Duchenne and limb-girdle and facioscapulohumeral muscular dystrophies, motor unit numbers are within the normal range, but are significantly reduced in myotonic muscular dystrophy.

The severity of denervation and the extent of compensatory reinnervation in a number of neuromyopathies was investigated using our computer-assisted motor unit counting and subtraction techniques. Patients with the chronic neuropathies of diabetes mellitus, renal failure and alcoholism, the acute neuropathy of the Guillain-Barré syndrome, and the neuronopathies of motor neuron disease and Alzheimer's disease were studied. Reinnervation in the uremic and alcoholic neuropathies was poor, and considerably less than that found in diabetic neuropathy. In general, the neuronopathies showed better reinnervation than the chronic neuropathies. In the acute neuropathy of the Guillain-Barré syndrome, reinnervation continued over periods of up to 7 years from the onset of the illness. Within this group some patients showed poor reinnervation, whereas in others we found that all of the electrophysiological parameters studied returned to normal, with concomitant remodeling of previously large motor units to normal size as reinnervation progressed.

The extent of axonal dysfunction in a group of patients with diabetes mellitus has been investigated using recently introduced quantitative techniques of electromyography. In 40 diabetic patients, estimates of motor unit numbers in the extensor digitorum brevis muscles and measurements of the parameters of electrically evoked motor unit potentials therein are presented, along with significant correlations between these parameters and motor nerve conduction velocities and distal motor latencies in the lateral popliteal nerves. The results indicate that axonal dysfunction and concomitant collateral reinnervation are prominent and integral features of the neuropathy of diabetes mellitus. Axonal dysfunction is present in proportion to and parallels the severity of the demyelinative lesion. It is also extensive in patients without clinical evidence of neuropathy in whom the accompanying collateral reinnervation is of sufficient magnitude to mask the clinical signs of motor involvement.

The motor unit content and the dimensions of individual motor unit action potentials were studied in 17 patients with acute idiopathic polyneuritis from one week to 9 1/2 years after the onset of the illness. An initial decrease in motor unit numbers is followed by a progressive increase with the passage of time from the onset of the illness. The latencies, areas, amplitudes, and durations of individual motor unit potentials were increased above normal values. The results suggest the presence of significant axonal damage in the majority of cases of acute idiopathic polyneuritis. The intramuscular nerve fibres are the site of most severe electrophysiological dysfunction in this study.

An on-line computer method is described for the isolation of single motor unit potentials, evoked by stimulation of the anterior tibial nerve at the ankle, from the compound action potential recorded from surface electrodes over the extensor digitorum brevis muscle. The latencies, durations, amplitudes, and areas of the potentials were measured in a group of control subjects and patients with myasthenia gravis. In myasthenic patients there is a significant reduction in the durations of motor unit potentials and a significant increase in latencies while their amplitudes and areas remain unchanged. The results are consistent with the presence of a `terminal neuropathy' in myasthenia gravis.

Electrophysiological and clinical assessment of recovery of function was undertaken on 34 median and 33 ulnar nerve which had been resutured after complete section three and a half months to 24 years previously. An evaluation of different methods of repair was attempted. Our results suggested that re-exploration of the site of suture is indicated in the absence of voluntary activity on needle EMG by seven months (12 months for grafts), of an electrically evoked muscle action potential, measurable distal motor latency, or motor nerve conduction velocity by 10 months (14 months for grafts), or of clinically detectable voluntary muscle movement by 10 months after suture. By present techniques of repair useful prognostic information cannot be obtained by a consideration of sensory parameters either clinical or electrophysiological.

Clinical and electrophysiological assessment of recovery of function are reported on 20 patients with median or ulnar nerve sections up to 53 months after surgical repair. Maximum improvement of sensory function was apparent by both methods of assessment at 15 months after suture, and thereafter conduction velocities in sensory fibres averaged 80% of normal in median nerves and 70% of normal in ulnar nerves. Similarly, the mean amplitude of the sensory action potential at the wrist remained depressed at 15% of control values. The clinical recovery of motor function pursued a similar time course with, however, some evidence to indicate a continuing improvement in the neurophysiological maturation of the motor nerve fibres up to 47 months after repair. The results are discussed in relation to previous electrophysiological studies on animals.