Referred pain from intraneural stimulation of muscle fascicles in the median nerve.

Microelectrode recordings were obtained from 118 cutaneous and 26 muscle fascicles in the intact median nerves of healthy human subjects. The exploring electrodes were also used for painful electrical stimulation of the identified fascicles. Cutaneous pain was accurately projected to fields within the median innervation territory. Deep pain was projected to muscles innervated by the median nerve, but in 7 experiments it was also segmentally referred to muscles in the ipsilateral upper arm, axilla or chest. Reaction time measurements indicated that referred pain was conveyed by afferent group III fibres from muscle, but did not exclude a possible contribution by group IV fibres. Referred pain was influenced by temporal and spatial summation of the afferent inflow. The magnitude of referred pain was positively correlated to the stimulation frequency of deep nociceptive fibres. The results from this study on experimentally induced pain confirm clinical observations of proximal referral of pain in patients with median nerve entrapment, and prompt consideration of possible involvement of nerve fascicles supplying deep structures in the forearm or hand in the differential diagnosis of pain in the chest and upper arm.

Central effects of zomepirac on pain evoked by intraneural stimulation in man.

The central analgesic activity of zomepirac was studied in six healthy subjects by means of intraneural electrical stimulation. Pain elicited by selective activation of nociceptive fibers was inhibited by the administration of a single oral dose of 100 mg zomepirac. Pain relief in this double-blind crossover study was significantly greater after zomepirac than after placebo. Maximal analgesic effect was observed between 30 and 90 minutes after ingestion. Since peripheral receptors are bypassed by this technique, it is postulated that the observed effect reflects a central action of zomepirac, possibly as a result of inhibition of prostaglandin synthesis in the central nervous system.

Peripheral projections of nerve fibres in the human median nerve.

Elementary sensations of definable quality were evoked by intraneural electrical stimulation of sensory units through tungsten microelectrodes inserted in the median nerve of awake human subjects. The most commonly reported sensations were tapping, pressure, dull pain and sharp pain, which correlated with recording from RA units, SA I units, C nociceptors and A delta nociceptors, respectively. All sensations were projected more often to the fingertips than to the palm. The multifocal projections of sensations recruited by excitation of small groups of neighbouring nerve fibres were significantly more scattered in space than anticipated if these fibres had preserved an orderly intraneural map, implying lack of somatotopy in the nerve. Mean projected field sizes were 3.4 mm2 for sharp pain, 9.2 mm2 for tapping/vibration, 29.3 mm2 for pressure and 35.4 mm2 for dull pain, and in addition the latter two showed a rising size gradient from fingertip to palm. Consideration of projected field size as a variable in discriminative touch suggests that input from RA units and A delta nociceptors may be of importance in stimulus localization, while SA I units may play an additional role in two point discrimination.

Favourable outcome in non-traumatic anterior interosseous nerve lesions.

Six patients with non-traumatic anterior interosseous nerve palsy are described. In five patients the onset was acute with upper arm pain, which peaked within 4 weeks and thereafter declined. Virtually complete spontaneous recovery occurred in all patients between 9 and 24 months. It is concluded that non-traumatic anterior interosseous nerve lesions are most likely to reflect a circumscribed form of brachial neuritis and that surgical decompression should be deferred for at least a year or indefinitely if recovery is proceeding.

Cutaneous localisation of laser induced pain in humans.

Localisation of painful laser-induced stimuli has been compared to localisation of tactile stimuli in normal humans. Laser stimulation evoked pain of two qualities (sharp pricking pain and hot burning pain). Sharp pricking pain was found to be localised with almost equal precision to tactile stimuli (13.8 +/- 3.4 versus 11.6 +/- 2.3 mm) on the dorsum of the hand, (21.5 +/- 7.9 versus 20.6 +/- 7.5 mm) on the forearm and (15.5 +/- 5.6 versus 13.8 +/- 5.4 mm) on the foot, respectively. There was no significant difference between the ability to localise tactile stimuli and hot burning pain except on the dorsum of the hand. These results indicate that tactile information is not essential for the accurate localisation of cutaneous pain.

The incidence of craniocervical bony anomalies in the adult Chiari malformation.

Detailed linear, angular and surface area measurements were undertaken on the lateral skull radiographs of 32 patients with proven idiopathic adult Chiari type 1 malformation. Basal angles were larger, the clivus was shorter and Klaus' index was reduced in patients compared to normal controls. The size of the posterior fossa was smaller in patients than in controls. By discriminant analysis of the skull X-ray data it was possible to identify correctly two thirds of patients as belonging to the patient group. The findings indicate that craniocervical bony anomalies in the adult Chiari malformation are commoner than was previously realised, and they support the view that tonsillar herniation in these patients results from bony occipital dysplasia.

Observations on severe ulnar neuropathy in diabetes.

We describe the clinical and neurophysiologic findings in a group of diabetic patients with a severe ulnar neuropathy. All patients attending a large inner-city diabetes center were prospectively screening for hand wasting and weakness due to ulnar nerve disease. Twenty diabetic patients fulfilling the clinical criteria underwent nerve conduction studies and electromyography. All but one patient with a motor ulnar neuropathy had systemic complications, mostly severe: ten were amputees, four had had a renal transplant, and two were blind. The onset of hand weakness was sudden in five. All patients had a classical "ulnar hand" (bilateral in five) but forearm muscles were little affected. Sensory loss was prominent in only one-half. Nerve conduction studies showed markedly reduced ulnar motor responses (mean, 1.2 mV versus 7.4 mV in controls) and ulnar/median motor ratios. Motor conduction was disproportionately slowed across the elbows, with or without conduction block, in only eight of 34 affected ulnar nerves. Five of these patients had a habit of leaning on their elbows and/or a Tinel's sign. Median sensory action potentials (SAPs) were recordable in 12 patients but ulnar SAPs were absent in 30 of 34 affected nerves. Electromyography revealed advanced denervation of ulnar supplied hand muscles. We conclude that motor ulnar neuropathy is not uncommon in patients with diabetes of long standing, especially in those with severe systemic complications. Nerve entrapment at the elbows occurs in some, but in many the lesion is axonal, and damage may occur through ischemia.

Computing in clinical departments: implications for the design of hospital information systems.

Information technology is of increasing importance to the health service. Two main types of system have grown up, those in clinical departments and central administrative systems. It is important to consider their inter-relationships. A clinical system in the Renal Unit at Manchester Royal Infirmary is described, which is typical of many departmental systems. Further work is reported demonstrating an impressive commonality in the requirements of different clinical disciplines and supporting the view that departmental systems are a valuable source of accurate management data. The experience gained from designing departmental systems is reviewed. It is concluded that the participation of users is essential to the successful design and implementation of systems in the National Health Service and that departmental systems have a crucial role to play in the development of district information systems.

On the choice of muscle in the electrophysiological assessment of myasthenia gravis.

We performed repetitive nerve stimulation on 38 adult patients with generalised myasthenia to compare the relative diagnostic yield from deltoid and trapezius. The decrement was consistently greater in deltoid, both before and after maximum voluntary contraction. In 12 patients the test was negative in trapezius but diagnostic in deltoid, whereas the converse occurred in only one. The yield from facial muscles was comparable to that from trapezius while that from hand muscles was very low. Post-tetanic exhaustion often enhanced the decrement but the use of stimulus frequencies greater than 2-3 Hz did not. We conclude that deltoid provides the highest diagnostic yield in myasthenia when doing decremental studies.

A quantitative study of sensory function in hereditary spastic paraplegia.

Somatic sensation was studied in 23 patients from 14 families with hereditary spastic paraplegia. Quantitative sensory testing revealed significantly raised thermal, heat pain, vibratory and tactile thresholds in patients as compared with normal controls. Cutaneous sensitivity was more severely impaired in the feet than in the hand. All patients had at least one elevated sensory threshold. Sensory nerve conduction studies were abnormal in 6 patients, 5 of whom were members of the same family. Somatosensory evoked potentials were reduced on average to half the size of those of controls. Although the clinical picture is dominated by a spastic paraparesis, subclinical sensory impairment is common in hereditary spastic paraplegia and may reflect involvement of peripheral nerves, afferent pathways in the spinal cord or both.

Changes in sensation after nerve injury or amputation: the role of central factors.

Dynamic changes in somatosensory cortical maps are known to occur in experimental animals subjected to peripheral nerve transection or amputation. To study the sensory effects of central nervous system adaptation to temporary or permanent loss of input from a part of the hand, multimodality quantitative sensory tests were carried out in 11 patients with complete traumatic division and repair of the median or ulnar nerves and in six patients who had undergone amputation of one or more digits. As expected, vibration, two point discrimination, and tactile thresholds were raised in the territory of the injured nerve in a graded fashion, sensitivity being poorest in the patients with the most recent injuries. Surprisingly, localisation was better in the tips than at the base of the hypoaesthetic fingers, suggesting a central attentional gradient. Stimulus-response curves conformed to a power function whose exponent was higher in denervated than in normal skin. Changes in psychophysical functions were also discernible in the intact hand. There was no hyperaesthesia in the territory of the nerve adjacent to the injured one or in the stump in the case of amputees. Central factors contribute to the sensory changes seen after nerve injury, but the functional effects of the cortical reorganisation that follows partial deafferentation are more subtle than a simple heightening of sensitivity in the surrounding skin.

Hereditary progressive chorea without dementia.

A family with hereditary non-Huntington's chorea is presented. Transmission was autosomal dominant with variable penetrance. Chorea commenced in childhood and affected predominantly the head, face and upper limbs. Dysarthria appeared later, followed in two family members by elements of an axial dystonia. There was no intellectual impairment. Unlike previously described families, symptoms progressed steadily up to the eighth decade, causing considerable physical disability.

Sensory neuropathy in hereditary spastic paraplegia.

A large kinship is reported with dominantly inherited spastic paraplegia starting in the first decade of life; its clinical evolution was indistinguishable from that of "pure" hereditary spastic paraplegia (HSP). However, all patients studied had electrophysiological evidence of a predominantly sensory polyneuropathy, which was confirmed on nerve biopsy in three. The histological findings indicated virtually complete loss of large diameter fibres with relative preservation of small myelinated and non-myelinated fibres. The neuropathy was largely asymptomatic and there were no trophic ulcers. This family represents a distinct entity which differs from other reported cases of HSP with neuropathy by virtue of the clinical predominance of the pyramidal syndrome, the greater impairment of large fibre sensory modalities than of pain or temperature modalities, and the consequent absence of mutilation.

Investigation of the functional correlates of reorganization within the human somatosensory cortex.

Much work in animals and humans has demonstrated the existence of changes in topographic organization within the somatosensory cortex (SSC) after amputation or nerve injury. Afferent inputs from one area of skin are able to activate novel areas of cortex after amputation of an adjacent body part. We have investigated the functional consequences of this reorganization in a group of patients with nerve injury. Using the microneurographic technique of intraneural microstimulation (INMS) we stimulated groups of nerve fibres, within individual fascicles proximal to the nerve transection, with small electrical pulses. This enabled us to activate the deafferented cortex that had presumably undergone remodelling and study the conscious percepts described by the subjects. In 39 fascicles from 10 subjects, we found that the sensations evoked on INMS were no different from those reported previously by subjects with intact nerves. This finding suggests that such reorganization within the SSC has little effect on the function of deafferented cortical neurones or subcortical relay stations. In a separate set of experiments, INMS was performed in 16 nerve fascicles from an adjacent non-injured nerve or uninjured fascicle within a partially injured nerve. The sensations evoked by INMS in these experiments were also comparable to those obtained in normal subjects. This indicates that the expanded cortical representation of adjacent non-anaesthetic skin does not influence the cortical processing of afferent information. Taken together, these findings lead us to question the notion that reorganization of connections within the somatosensory cortex equates to a change in function. Whilst it may be advantageous that the human brain is not 'hard-wired', neurophysiological proof of functional plasticity in the adult somatosensory system as a result of deafferentation is elusive.

Projected and receptive fields: a comparison of projected areas of sensations evoked by intraneural stimulation of mechanoreceptive units, and their innervation territories.

Microneurography and intraneural microstimulation were employed in awake human subjects to study the characteristics of cutaneous mechanoreceptive units and the sensations mediated by them. 172 units innervating the hand and forearm were identified as either PC, RA (FA in hairy skin), SA I or SA II. Analysis of action potential waveforms in a sample of units suggests that most recordings were from within the myelin sheath. Receptive fields of RA and SA I units were significantly smaller than those of PC and SA II units and showed a proximodistal size gradient, which the latter two did not. The quality of sensations evoked by intraneural stimulation was determined by the type of unit activated, except in the case of SA II units, and their magnitude could be influenced by mechanical coactivation of other sensory units. As a rule projected fields of evoked sensations were larger the further away they were from the limb tip. This grading indicates that inputs from single mechanoreceptive units are processed differently according to their source and sensory submodality, possibly as a result of unequal "resolving powers" of the corresponding cortical neurons.

A new method for demonstration of central effects of analgesic agents in man.

A new method of eliciting experimental pain in man is described. Microelectrodes are inserted percutaneously into the peripheral nerves of awake subjects, and are positioned close to nociceptive fibres in order to elicit pain during intraneural electrical stimulation. Under fixed stimulation conditions the estimated magnitude of evoked pain remains relatively stable, unless a high stimulus frequency is used, which may lead to excitation failure of nociceptive fibres. This method can be employed to test for possible central modulation of pain, for instance by analgesic agents, since peripheral receptors are bypassed.