A human experiment in nerve division/Chapter 1
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IT had long been recognized that the consequences of injury to a peripheral nerve could not be adequately explained on any accepted theory of its structure and function. In 1901, Dr. Head and Mr. Sherren therefore determined to make a systematic examination of the patients attending the London Hospital for some nerve injury. The hospital patient is frequently an admirable subject for sensory experiments; at his best he answers "Yes" and " N o " with certainty, and is commendably steady under the fatigue of control experiments. Moreover, the number of patients, who come to the London Hospital for such injuries, is so large that it is possible to eliminate entirely those who are found to be untrustworthy in consequence of misuse of alcohol or other causes.
Most of the main facts of nerve distribution and recovery of sensation can be elicited from a study of hospital patients by means of simple tests requiring no undue expenditure of time. But such patients can tell little or nothing of the nature of their sensations, and the time they are able, or willing, to give is insufficient for elaborate psycho-physical testing. It soon became obvious that many observed facts would remain inexplicable without experimentation carried out more carefully and for a longer period than was possible with a patient, however willing, whose ultimate object in submitting himself to observation is the cure of his disease. For instance, an examination of the part played by heat- and cold-spots in the return of sensation was impossible under clinical conditions.
It is also unwise to demand any but the simplest introspection from patients, to whatever class they may belong. This side of the investigation was, therefore, almost entirely closed to Mr. Sherren and Dr. Head. From the early days of their research, Dr. Rivers had acted as their guide and counsellor. His interest lay rather in the psycho-physical aspect of the work, and he was impressed with the insecurity of this side of the investigation. Introspection could be made fruitful by the personal experiences of a trained observer only.
Lastly, we were anxious to investigate the functions of deep sensibility. Sherrington had shown that muscular nerves contained a large number of afferent fibres. From the beginning of their research, Head and Sherren had tried to determine the sensibility remaining after complete division of all cutaneous nerves without injury to the muscular branches. But accidental injuries of this kind are excessively rare, and they were compelled to attack the problem by indirect and less satisfactory methods. As soon, therefore, as it was determined to make an experimental division of peripheral nerves, means were taken to ensure that the nature of these deep afferent fibres should come clearly to experimental investigation.
At the time of the experiment, H. was nearly 42 years of age and in perfect health. Since boyhood he had suffered from no illnesses, excepting as the consequence of wounds in the post-mortem room. None of these had attacked his left arm or hand, which were entirely free from scars or other deformities.
For two years before these experiments began he had given up smoking entirely. No alcohol was ever taken on the days during which he was under examination, and for some years he had abstained from alcohol except on holidays.
On April 25, 1903, the following operation was performed by Mr.Dean, assisted by Mr. Sherren. (To Mr. Dean our best thanks are duo, not only for the exactitude with which he carried out our wishes, but also for his kindness in receiving Dr. Head into his house for the operation.)
An incision 6 1/2 in. (16'5 cm.) long was made in the outer bicipital fossa extending along the axial line of the left upper extremity ; this wound was almost exactly bisected by the fold of the elbow. After turning back the skin, the supinator longus was hooked outwards, and the radial nerve (ramus superficialis nervi radialis) was divided at the point where it arises from the musculo-spiral (N. radialis). A small portion was excised, and the ends united with two fine silk sutures. The external cutaneous nerve (N. cutaneus antibrachii lateralis) was also divided where it perforates the fascia, above the point where its two branches are given off to supply the anterior and posterior aspects of the pre-axial half of the forearm. The nerve was sutured with fine silk, and the wound was closed with silk sutures, without drainage. The limb was put up on a splint with the forearm flexed at the elbow, and the whole hand was left free for testing. The wound healed by first intention.
The following morning (April 26, 1903), the radial half of the back of the hand and dorsal surface of the thumb were found to be insensitive to stimulation with cotton wool, to pricking with a pin, and to all degrees of heat and cold. Around the base of the index and middle fingers was a small area insensitive to stimulation with cotton wool and von Frey's hairs, where a response was obtained to the prick of a pin. No sensation was evoked by any manipulation of the hairs within the affected parts on the back of the hand.
The area insensitive to cotton wool extended slightly further towards the ulnar aspect of the back of the hand than that of the cutaneous analgesia. Between the two lay a narrow zone, where a painful cutaneous stimulus produced a more unpleasant sensation than over the normal skin.
The most striking fact, however, was the maintenance of deep sensibility over the whole of the affected parts on the back of the hand. Pressure with the finger, with a pencil, or any blunt object was immediately appreciated. All those stimuli commonly used by the clinician to test the presence of " touch " were appreciated and well localized. Mr. Dean, who was not familiar with our previous observations, said he should ha've thought that sensation of touch was intact, had he not known the nerves had been divided.
On May 4, nine days after the operation, the hand was exposed to a long series of experiments. The most striking features of this examination were :—
(a) That very moderate pressure on the abnormal area of the skin was appreciated and could be well localized, whilst touches with cotton wool, or deformations of the skin, produced by drawing the hair outwards caused absolutely no sensation.
(b) In spite of the existence of this sensibility, two compass-points could not be distinguished, even when separated by 8 cm.
(c) All sensation was lost to cutaneous painful stimuli, and to heat and cold. In fact, the condition might easily have been mistaken for one of analgesia and thermo-anaesthesia with intact sensibility to touch.
(d) Between the extent of the analgesic area and that insensitive to cotton wool, lay a border where the prick of a pin was abnormally painful.
(e) None of the cold-spots marked out before the operation reacted to the usual stimuli.
By May 4 the skin on the back of the hand had assumed a peculiar condition, which was described on the 7th by Dr. J. H. Sequeira in the following words:—
"The whole of the affected area is of a slightly deeper red than the rest of the skin of the hand. It is dry, and covered with minute hairlike scales. On palpation, the skin appears to be thickened and looks as if it were slightly oedematous; but it does not pit on pressure. A striking feature is the absence of the normal elasticity, which is in remarkable contrast with the rest of the skin. The affected parts do not sweat, while the rest of the hand is permanently slightly moist."
From the time of the operation until the removal of the splint (May 23), the borders of the loss of sensation on the forearm underwent no material change. But H.'s skin has always been peculiarly susceptible to the action of chemical antiseptics, and the necessary cleansing at the time of the operation led to desquamation to within about 3 in. to 4 in. of the wrist. Fortunately, the hand had entirely escaped their action.
On the extensor aspect of the forearm, the loss of all forms of cutaneous sensation was bounded for the greater part by a definite line. Towards the radial aspect, the loss of sensation merged more gradually into parts of normal sensibility. The borders formed a sinuous line, seen on figs. 3 and 4. Over the greater part of the forearm, the loss of sensation to prick was less extensive than that to cotton wool; but nearer to the wrist, the reverse condition seemed to exist.
The extent of the cutaneous analgesia on the hand was slightly less than that of the loss of sensation to cotton wool and von Frey's hairs, and to these stimuli all the boundaries were sharply defined, except at the base of the index and middle fingers.
The splint was removed on May 23, and it was then possible to wash the arm vigorously and to remove the loose scales of epithelium. We then discovered that the loss of sensation to prick was everywhere coterminous with, or slightly less extensive than, the loss to cotton wool, except near the wrist. Here there was a triangular area, shown on fig. 5, where cotton wool and No. 5 of von Frey's hairs were undoubtedly appreciated, although the skin was insensitive to prick.
On the back of the hand, sensibility remained exactly in the condition described immediately after the operation. Over the whole area of cutaneous anaesthesia, pressure-touches were appreciated and well localized. Pain could be produced as easily by pressure with the algometer over the back of the affected as over similar parts of the normal hand. Electrical stimuli produced no sensation except when the muscles contracted; then the smallest visible movement was appreciated. To recognize pure movement, produced electrically, without a concomitant cutaneous sensation is a remarkable experience.
Though sensitive to the tactile and painful elements of pressure, and to the passive movement of muscles, the back of the hand was anaesthetic to all thermal stimuli; the tissues could be frozen firmly with ethyl chloride without the production of even the slightest sensation.
The first noticeable change in the extent of the loss of sensation was discovered on June 7, forty-three days after the operation. The borders of the area insensitive to cotton wool remained unaltered, but the cutaneous analgesia was distinctly less extensive, and no longer coincided with it on the flexor aspect of the forearm; the extent of the cutaneous analgesia had diminished for 3 in. (8 cm.), or more, peripheral to the scar. This was particularly noticeable, because the borders of the loss of sensation to cotton wool had remained unchanged.
Moreover, the boundaries of the cutaneous analgesia were no longer definite, but were made up of islets, or points, of sensation. Passing from the area of complete loss to parts normally sensitive to a prick, the pin struck spots, where it produced a slowly developed, dull but painful sensation. If, however, this particular spot was not struck, it might be that sensibility was not encountered until another spot was reached, some millimetres nearer the unaffected parts of the limb.
On June 14, fifty days after the operation, the gradual shrinking in extent of the cutaneous analgesia on the arm was found to have continued (figs. 6, 7 and 8), although the borders of the loss of sensation to cotton wool remained entirely unaltered. The loss of sensation to cold corresponded in extent with that of the loss to prick; but, wherever the part was feebly sensitive to 'the latter stimulus, sensibility to cold seemed to be absent. To all degrees of heat the borders of the loss of sensation had remained unchanged, and the extent of the anassthesia, even to temperatures between 50° C. and 60° C, uniformly exceeded that of the loss to prick.
On the flexor surface of the .forearm, there was nothing to show that cold could be appreciated within the border of cutaneous tactile anaesthesia. In the first interosseous space, cold was certainly appreciated well inside the limits of the loss of sensation to cotton wool; the border of the loss to cold lay about midway between that for cotton wool and that for prick.
By July 20 (eighty-six days after the operation), there was no part of the forearm where a prick could not be occasionally appreciated, although in many places this form of sensation was extremely defective. Moreover, considerable changes had occurred in the condition of the hand ; the whole of the thumb and the skin over the radial half of the first metacarpal had become sensitive to prick. The analgesic area on the back of the hand was diminishing from its radial aspect.
In spite of these changes, the borders for the loss of sensation to cotton wool remained exactly as before.
On the forearm, ice was not appreciated with certainty, until the original border of cutaneous analgesia was passed. Water above 50° C. produced pain within the parts now sensitive to a prick, but it was impossible to say whether the pain was accompanied by any thermal quality.
The terminal phalanx of the thumb was certainly sensitive to cold below 17° C. and more doubtfully to heat above 45° C. Within the area of dissociated sensibility in the first interosseous space, and over the ball of the thumb, it was difficult to be sure that any sensation of temperature was produced by ice-cold and hot water; but the border of the thermo-ansesthesia probably lay slightly within that for sensibility to cotton wool.
At this time, some of the hairs on the forearm within the affected area became sensitive to pulling. The sensation produced was slowly developed and excessively unpleasant. It died away, and recurred again, without further stimulation. Those hairs lay entirely within the upper antesthetic patch.
On August 10 (107 days after the operation), the sensibility to prick had further improved, although the extent of the anaesthesia to cotton wool remained entirely unaltered. On August 15, for the first time since the recovery of sensation began, it could be said that parts which were at first insensitive to heat and cold now responded definitely and constantly to these stimuli. Over the upper patch on the forearm, ice uniformly produced a sensation of cold. Temperatures above 50° C. caused a stinging sensation, usually called " burning," but it is doubtful to what extent this contained more than the painful element of heat.
The terminal phalanx of the thumb undoubtedly responded to temperatures above 45° C, and the sensation produced by temperatures above 50° C. contained a thermal element in addition to the stinging pain. Even the proximal phalanx of the thumb had become sensitive to ice, although still anassthetic to heat.
On August 15 and 16, these observations on the upper patch of the forearm and the terminal phalanx were confirmed, and within these areas we were able to mark out definite cold-spots for the first time since the operation. Four of these lay in the upper patch, and four over the terminal phalanx of the thumb.
By September 9 (137 days after the operation), the whole forearm had become sensitive to cold, and cold-spots were discovered not only in the upper patch on the forearm and in the terminal phalanx of the thumb, but also over the more distal portions of the affected area. The forearm still remained insensitive to heat, except in as far as temperatures above 50° C. produced a peculiar form of painful sensation, usually called "burning."
In spite of the complete absence of any change in the behaviour of the affected parts to cotton wool, sensibility to prick continued to return steadily, and by September 24 (152 days after the operation) a small area only on the back of the hand remained insensitive to this stimulus (fig. 11).
Since July 10, when the back of the hand had been too energetically frozen with ethyl chloride, an indolent sore had existed in the centre of the affected area. It tended to heal if protected, but would break down again under the influence of the slight accidents of ordinary life. On September 23, attention was attracted to its condition by the presence of tingling, which had never been noticed before. This led to the discovery that painful sensation, of a dull and ill-defined character, was present in the neighbourhood of the sore. From this time it healed with great rapidity, although no special care was taken to protect it. Once healed, it never broke down again after the return of sensibility to painful cutaneous stimuli.
About this time, part of the first interosseous space, which had become sensitive to prick, began to respond to ice; this return of sensation was found to be associated with a few definite cold-spots. But the affected area still remained insensitive to heat.
On October 3 (161 days after the operation), we noticed, for the first time, that cotton wool produced some sensation over the upper patch on the forearm. This change advanced with considerable rapidity, and on October 6 sensibility to cotton wool was present in a very defective form over both upper and lower forearm patches. The upper of these areas seemed to become sensitive by gradual encroachment from the edges, whilst the lower appeared to recover at the centre as quickly as at the periphery. Later we found that this response was due entirely to the return to the hairs of a peculiar form of sensibility.
About this time (October 8), the upper patch on the forearm became undoubtedly sensitive to temperatures of and above 45° C. An excellent heat-spot was found in the centre of the patch, to which this return was certainly due.
By October 15 (173 days after the operation), no part of the hand was entirely insensitive to prick, although sensation was defective over the parts dotted on fig. 12.
The greater part of the back of the hand now reacted to the more extreme degrees of cold, and the cold-spots had multiplied greatly. By November 1 (190 days after the operation), cold could be appreciated everywhere over the back of the hand, and twenty-four cold-spots were discovered within the affected area. At the same time, one heat-spot was found near the base of the first phalanx of the thumb. This was the only part of the affected area on the hand sensitive to heat.
From this time, the cold-spots and heat-spots rapidly increased in number over the back of the hand, the increase proceeding step by step with the recovery of sensibility to cold and to heat.
With the gradual return of sensibility to pain, cold, and heat, we noticed that the sensation tended to be widely diffused, and was not infrequently localized in some part remote from the point of stimulation (September, 1903). If, for instance, ice was applied to the proximal portion of the forearm, a sensation of coldness was produced in the thumb. The site of this referred sensation remained the same, whatever the nature of the stimulus, provided it was one to which the affected area had become sensitive.
By December 3 (222 days after the operation), the peculiar tingling sensation produced by cotton wool could be .evoked by stimulating the thumb and the adjoining interosseous space. This sensibility rapidly increased in extent, until there was scarcely any part of the affected area from which it could not be produced (December 6). The sensation was one which could be expressed only as a general state of diffuse painless tingling. Moreover, it was found that parts which gave this reaction to cotton wool were insensitive to No. 5 of von Prey's hairs and to the painless interrupted curi'ent, just as in the early days after the operation. Exactly the same borders could be marked out both on the forearm and hand by dragging a pin lightly from normal to abnormal parts; for as soon as the old border of cutaneous anaesthesia to touch was passed, the sensation became a widely diffused tingling pain.
Thus it would seem that the sensibility to cotton wool, which began to return to the forearm 161 days, and to the hand 224 days, after the operation, was not the equivalent of the normal sensation of light touch over hairless parts, but was a peculiar form of hair-sensibility. For the areas endowed with it remained anaesthetic to the painless interrupted current and to No. 5 of von Frey's hairs; moreover, the sensation produced was widely diffused and was referred to remote parts, exactly like the sensation of prick and ice-cold over the same regions. This hypothesis was found at a later date to be correct. For on shaving the areas endowed with this form of sensibility, they became entirely insensitive to cotton wool.
We could not be certain that the forearm was sensitive to cotton wool when carefully shaved, until April 24, 1904, exactly a year after the operation.
On June 5, 1904 (407 days after the operation), the affected area on the forearm responded to temperatures of 37° C. This sensibility to warmth rapidly increased, and on June 26 was obtained, even with 34° C. Moreover, the sensation produced was one of warmth localized in the part touched. Except that it was not quite so acute, it exactly resembled that produced on the normal skin under similar circumstances. It had none of the diffuse radiation and tendency to reference into remote parts, so characteristic of the sensation evoked by stimulating heat-spots.
It was not until November 12, 1904 (5G7 days after the operation), that a portion of the back of the hand (fig. 13) began to be undoubtedly sensitive to warmth (35'5° C.) and to cotton wool after shaving. The diffusion and radiation so characteristic of the previous stage of recovery were at once greatly diminished; so profound was this change that we recognized it before we could be certain of the increased sensibility to thermal and tactile stimuli.
Up till the end of November, 1904, the- improvement continued rapidly. But with the advent of winter cold the condition of the hand went back; the referred sensations reappeared, to become as definite as they had been six months before, and the hand became less sensitive to warmth and to cotton wool after shaving.
In March, 1905, it again began to improve. Part of the affected area on the back of the hand became sensitive to No. 5 of von Frey's hairs, and reference greatly diminished. By May 21, a large area on the back of the hand had become sensitive to cotton wool and to minor degrees of heat; stimulation with No. 5 was widely appreciated. A referred sensation could no longer be produced from any part in this condition.
Although this improvement continued throughout the summer of 1905, a small portion of the affected area, lying mainly in the neighbourhood of the knuckles of the index and middle finger, has remained insensitive to No. 5, or to cotton wool after shaving (fig. 14). Even at the present time, this part still is in a purely protopathic condition, sensitive to prick, to ice and to water above 37° C. All these stimuli cause sensations, referred to the dorsal aspect of the thumb and diffused widely around the point to which they'are applied. It seems as if one of the branches of the external cutaneous had not reunited, leaving this part of the affected area to be supplied by its fellow and by the' radial.
The history of the case may be summed up in the form of the following diary :—
On April 23, 1903, the radial (ramus superficialis nervi radialis) and both branches of the external cutaneus (N. cutaneus antibrachii lateralis) were divided in the neighbourhood of the elbow. Both nerves were reunited with silk sutures and the wound healed by first intention.
This operation did not interfere with sensibility to the tactile and painful aspects of pressure. But the whole of the affected area became insensitive to prick, to heat, and to cold ; two points of the compasses, applied simultaneously, could not be appreciated, but localization was preserved.
Forty-three days after the operation (June 7), the extent of the cutaneous analgesia had begun to diminish.
Fifty-six days after the operation (June 20), the analgesia on the forearm had greatly diminished, and the thumb had become sensitive to prick.
Eighty-six days after the operation (July 20), the whole forearm responded to prick, and the back of the hand was becoming rapidly sensitive to this form of stimulation. Cold was not appreciated except over the terminal phalanx of the thumb, and 50° C. gave rise to no sensation of heat.
One hundred and twelve days after the operation (August 15), the proximal part of the affected area over the forearm had become sensitive to cold.
One hundred and thirty-seven days after the operation (September 9), the whole forearm had become sensitive to cold.
'One hundred and fifty-two days after the operation (September 24), the whole of the affected area, excepting a small spot on the back of the hand, had become sensitive to prick; the trophic sore healed.
One hundred and sixty-one days after the operation (October 3), cotton wool began to produce a diffuse tingling sensation over the forearm when the hairs were stimulated, but the whole of the affected area still remained insensitive to von Frey's tactile hairs. About the same time, the proximal patch on the forearm began to be sensitive to heat, and a definite heat-spot was discovered in this position.
One hundred and seventy-three days after the operation (October 15), the whole of the back of the hand had become sensitive to prick and, in a less degree, to cold.
One hundred and ninety days after the operation (November 1), the first heat-spot was discovered on the back of the hand.
Two hundred and twenty-five days after the operation (December 6), the hairs on the back of the hand responded with a diffused tingling to cotton wool, but the whole affected area of the forearm and hand still remained insensitive to von Frey's tactile hairs. This sensibility to cotton wool disappeared at once, if the arm was carefully shaved.
Three hundred and sixty-five days after the operation (April 24,1904), the proximal patch on the forearm began to be sensitive to cotton wool after shaving.
Between four hundred and seven and four hundred and twenty-eight days after the operation (June 5 to June 26, 1904), the affected area on the forearm became sensitive to temperatures between 37° C. and 34° C. The tendency to diffusion and reference greatly diminished.
Five hundred and sixty-seven days after the operation (November 12, 1904), the greater part of the affected area on the back of the hand had become sensitive to cutaneous tactile stimuli, and temperatures below 37° C. evoked sensations of warmth.