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Chapter VII Autonomic Recovery Bertram Selverstone and James C. White A. INTRODUCTION Recovery of autonomic function has been assessed and compared in the various nerves by means of certain simple subjective and objective criteria. An attempt has been made to determine which characteristics of the in- jury itself and of its treatment may influence the degree of functional recovery to be expected. The effects of level of injury, associated injuries to major arteries, bones, and joints, time of operation, length of gap, suture material, and other features of the nerve wound and of its operative treatment have been viewed in the light of statistical analysis divorced, insofar as possible, from the preconceptions of the authors. An attempt has been made also to study the relations among the indices which have been used to assess autonomic recovery and to determine the relation of recovery of autonomic functions to those of sensation and motor power. At follow-up, each veteran was asked a number of questions designed to elicit complaints which might have resulted from failure of normal auto- nomic recovery. The only complaint studied which is clearly attributable to impairment of autonomic recovery was that of loss of sweating. Although data are available concerning the complaint of excessive sweating, such data are indicative only of reinnervation of sweat glands; an excessive amount of secretion has no known relation to autonomic recovery unless it is clearly limited to the distribution of a specifically injured nerve, as in the auriculotemporal syndrome. The present data were not gathered with this point in mind. In the authors' opinion this complaint of exces- sive sweating in a wounded veteran most often results from general auto- nomic stimulation related to anxiety. Data have also been accumulated concerning the complaint of abnormal sensitivity to extremes of tempera- ture. Here again, there is no clear relationship between this complaint and autonomic recovery. While in certain experimental animals sympa- thectomy may be followed by an abnormally intense vasoconstrictor response because of sensitization of arteriolar walls to circulating epine- phrine and sympathin, recent work summarized by White, Smithwick, and Simeone (85) indicates that the phenomenon is barely detectable in man. Obvious cooling of the extremities is, however, a common finding after a major nerve injury with incomplete recovery. Doupe (20) has discussed this phenomenon in humans, but suggests that a more important mechanism is the reduced metabolism of paretic striated muscle. Ml

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Objective criteria of autonomic recovery depend upon determinations of skin resistance by the methods of Richter (63) and, less often, of sweating by the starch-iodine method of Minor (52) or the quinizarin test of Gutt- mann (31). Plethysmographic studies for return of vasomotor activity were not undertaken. There is, however, no evidence fur ciisassociatijn between sudomotor and vasomotor recovery, and individuals with clearly elevated skin resistance or absence of sweating in the distribution of an injured nerve may be classified as failures insofar as autonomic recovery is concerned. Certain differences, both anatomical and physiological, will be recalled between sympathetic innervation and that of the somatic motor and sen- sory systems. The sympathetic fibers in the mixed peripheral nerves are unmyelinated or poorly myelinated fibers of small diameter, correspond- ing to conduction times of 0.5 to 1.0 meter per second. The peripheral structures chiefly influenced by these impulses are the blood vessels of the muscles and more especially of the skin, the sweat glands and the arrectores pilorum, which produce the phenomenon of "goosefksh" in man. Chemical mediation of autonomic impulses both at ganglia and at end- organs, although less important in man than in lower animals, may permit singularly widespread activity by a few residual or regenerating axons. Furthermore, the peripheral distribution of the autonomic impulses is far more diffuse than that of the somatic impulses. When a peripheral nerve is severed, its autonomic fibers undergo Waller- ian degeneration in a manner similar to somatic fibers. Suture is followed by more or less regeneration in accordance with the classically accepted pattern for motor and sensory axons. There is no evidence to suggest, in their reaction to injury or in their ability to regenerate, that individual autonomic axons differ in any significant way from those of the somatic system. It is likely, however, because of the overlap of their peripheral innervation, that recovery of a relatively small proportion of the inter- rupted autonomic fibers of a nerve may produce complete recovery, both of symptoms and of measurable functional activity. B. DESCRIPTIVE DATA ON AUTONOMIC RECOVERY As in the earlier chapters, the tables for this section were confined to the representative sample. All seven major nerves were studied, but certain combinations of injured nerves and cases with sympathectomy were dropped. In the selection of combinations of injured nerves emphasis was placed upon pure lesions and upon median lesions accompanied by other nerve lesions; in addition, all sciatic lesions studied here involved both branches. Peroneal lesions with associated tibial lesions were also included. The criteria chosen as indicative of partial or complete persistence of loss of autonomic function after nerve injury are as follows: (1) Complaint of "loss of sweating." The assumption must be made that a ran- domly selected majority of patients have factual bases for this complaint. 342

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(2) Evidence of increased skin resistance in (a) the total area of innervation of the nerve, or (b) the assumed autonomous area of its distribution. (3) Evidence of absence of sweating in (a) the total area of the nerve, or (b) the assumed autonomous area of its distribution. Table 199 contains the data on these indices for sutured nerves. The complaint of loss of sweating appears to be much less common in association with pure radial nerve injuries than with injuries of the median, ulnar, sciatic, tibial, or peroneal nerves. This observation is consistent with data indicating that elevation of skin resistance is much less frequent with pure radial than with other major nerve lesions. It may not be concluded from these data, however, that a high degree of recovery of impaired autonomic function occurs after lesions of the radial nerve. It seems likely that radial lesions may be associated with relatively little initial disturbance of autonomic funetion. Proof of this hypothesis would re- quire preoperative studies similar to those which have been carried out in these follow-up examinations. Such data are not available. An alterna- tive explanation, not susceptible of proof or disproof here, would suppose a specific tendency for autonomic overlap from median and/or ulnar distributions in the presence of radial autonomic paralysis. Table 199.—Percentage of Cases With Evidence for Impaired Autonomic Recovery After Suture of Various Nerves Complaint of "loss of sweating" Increased skin resistance Objective loss of sweating Nerves injured Total area Autono- mous area Total area Autono- mous area Mecli.m orly 5.4 2.4 1.2 8.5 3.6 9.9 9.1 11.7 9.7 10.3 13.1 1.7 19.0 11.5 24. 1 9.4 23.6 9.1 25.3 31.6 8.6 32.1 21.8 27.7 26.4 31.5 18.2 9.1 11.5 0 16.0 25.0 37.9 47.4 36.0 50.0 22.7 17.3 20.0 24.0 33.3 27.6 15.8 24.0 33.3 Ulnp.r oi^Iy Radial only MicHan plus ulnar* radial, or both. . Pcrorcal only PtrorccJ plus tiLial ... Autonomic status is objectively superior in patients whose nerve injury was such as to have required lysis rather than suture. This conclusion emerges clearly from a consideration of the data concerning elevated skin resistance in table 200. Complaint of loss of sweating is no more frequent r.fter suture than after lysis, however, nor do the relatively fragmentary 343

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data derived from sweating tests disclose a difference between the two groups. Results of neurorrhaphy for an initially complete nerve wound do not differ from those after resection of a neuroma in continuity. As- sociated injury to radial or ulnar nerves does not affect the observed degree of recovery after median nerve injury; autonomic recovery following peroneal suture, similarly, is unaffected by the presence of associated tibial lesions. It would therefore appear, for nerves heavily supplied with autonomic fibers (i. e., other than the radial), that associated nerve injury is without effect on autonomic recovery. Table 200.—Percentage of Cases With Elevated Skin Resistance at Follow-up Examination, After Nerve Suture or Lysis Nerves injured Total area Autonomous area Complete suture Lysis Complete suture Lysis Median and ulnar (all cases) 13.8 1.6 10.5 23.9 7.5 0 0 10.9 30.2 9.5 18.8 0 | 26.4 9.8 C. INFLUENCE OF CHARACTERISTICS OF INJURY Certain characteristics of the patient and of his original nerve injury have been studied in order to determine whether they exert a significant effect upon the indices of autonomic function discussed in the previous section. All complete sutures on the median, ulnar, tibial, and sciatic- tibial nerves entered into the analysis except those in men with sympa- thectomies. Gross site of injury appears to have some relation to the chance of autonomic recovery, an elevated SR being more often found in a high suture than a low. Some suggestion of the same effect is also contained in the small amount of data derived from tests of sweating but complaints of loss of sweating do not vary by site. Associated injuries to bones and joints bear no consistent relation to any of the indices of autonomic recovery. More surprising, perhaps, is the observation that the presence of associated soft tissue defects sufficiently extensive to require plastic procedures do not significantly affect recovery of autonomic function. Infection severe enough to delay operation was uncommon but, insofar as data are available, it does not appear to exert a significant effect. Median and ulnar injuries were studied in order to determine whether associated major arterial ligations might influence autonomic recovery. No effect was noted upon the indices employed in this study. 344

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The age distribution of these men, most of whom had been wounded in battle, is not wide enough to permit definite conclusions concerning the effect on age on autonomic recovery. No evidence for such an effect has been observed. When wounds caused by shell fragments and other missiles were com- pared with those relatively few injuries produced by cutting instruments, no significant difference was found in autonomic recovery. D. INFLUENCE OF TECHNICAL ASPECTS OF MANAGE- MENT Certain technical features have long been considered, a priori, to be of importance in the result to be expected from a neurorrhaphy. The validity of these preconceptions has been subjected to statistical analysis in all the complete neurorrhaphies on the median, ulnar, tibial, and sciatic-tibial lesions in the series except those of men with sympathectomies. It must be emphasized that the results reported in this chapter are based upon evidence for autonomic functional recovery alone; they do not necessarily reflect the quantitative aspects of anatomic regeneration. The training of the surgeon credited with a neurorrhaphy was found to be uncorrelated with the result of the procedure. This observation must be interpreted in the light, however, of the special circumstances surround- ing this entire group of cases, described on pages 44-45. Surprisingly enough, features as discouraging as a delay for as much as 6 to 12 months between injury and operation, the recognition of excessive tension on the suture line, or the necessity for transposition, extensive mobilization or even a preliminary bulb suture are not correlated with evidence of impaired autonomic recovery. On the other hand, the ob- servation at operation that the condition of the nerve ends was "poor" or "very poor," although it is not associated with an increased incidence of complaints of diminished sweating, is correlated with elevated skin resistance at follow-up study. A similar situation is noted with respect to the adverse effect of multiple operations upon autonomic recovery. In the sciatic-tibial nerve at least, excessively long gaps are also associated with an increased incidence of elevated skin resistance at follow-up examina- tion. The materials and technique of the actual nerve suture showed certain positive correlations of interest. While the use of a stay suture has no discernible effect on autonomic recovery, skin resistance studies indicate that the use of a tantalum cuff is significantly advantageous. The choice of suture material appears to have no effect upon the reestablishment of normal skin resistance. As first analyzed, the data showed proportionately many more instances of increased skin resistance among plasma glue cases, but when the comparisons were refined, as in the earlier chapters, to take account of important differences in the cases to begin with, the inferiority of the plasma glue cases no longer seemed statistically significant. 403930—57 24 345

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It appears desirable to reiterate that the several indices of autonomic recovery provide only a gross indication of the anatomic regeneration of autonomic fibers. The relatively diffuse character of the chemical stimula- tion of autonomic end-organs by the nerve impulse (13) may m.ke it possible for regeneration of a few axons to be associated with functional recovery indistinguishable from that produced by complete regeneration. E. AUTONOMIC RECOVERY AND OTHER EVIDENCE OF REGENERATION Objective evidence of autonomic recovery is closely correlated with some aspects of recovery of somatic function. There is a suggestion that patients with the best sensory return complain least often of loss of sweating, but this association is not marked. The British summary of sensory return, however, is quite significantly associated with recovery of nDrmal skin resistance. Sweating tests, although done on relatively few patients, confirm this observation. The correlation between the British summary of motor recovery and recovery of normal skin resistance is hi^'n for thi median and ulnar nerves, but not for the tibial and sciatic-tibia!, perhaps because the observations are few in number. F. RELATION BETWEEN SUBJECTIVE AND OBJECTIVE EVIDENCE OF AUTONOMIC RECOVERY The complaint of loss of sweating, a considerable body of objective evidence derived from measurements of skin resistance, and a limited series of observations of objective evidence of sweating constitute the principal data. Information is also available with regard to complaints of increased sweating and of adverse reaction to heat and cold, but has not been used in the analysis since no clear relationship is known to exist between these complaints and recovery of autonomic function. The complaint of loss of sweating, which should be the most valid subjective index, was found to be significantly correlated with elevated skin resistance, but the relationship is not an intimate one. For example in the ulnar nerve, where the number of observations is large and the association of greater reliability, the complaint was registered by 12 percent of the men with increased SR in contrast to 5 percent of those with normal or decreased SR. A complaint of adverse reaction to extremes of temperature as might be expected was not found to be related in any way toSR. The meaning of the complaint of increased sweating is not entirely clear. The recording of this subjective complaint does not specify whether it was limited to the specific area of autonomic denervation. The complaint may have resulted from sympathetic discharge in areas of the injured extremity supplied by other nerves or even to generalized sweating associated with emotional tension. However, an initial impression that this complaint 346

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might be related to a need for psychotherapy, as indicated by the examiner's opinion or by the patient's estimate of himself as unemployable, is not borne out by statistical analysis. Furthermore, men who were considered by exarriners to be in need of psychotherapy were no more likely to com- plain of excessive sweating than the group as a whole. As would be expected, the complaint occurs less often in patients with increased than in those with normal or decreased skin resistance. In addition, there is a slight suggestion that the complaint occurs more often in men with decreased skin resistance. Increased skin resistance is known from many experimental observations to be a reliable index of loss of autonomic function. No data from this study have cast doubt on this observation. Decreased skin resistance, on the other hand, is not significantly correlated with any of the listed com- plaints, nor with objective tests of sweating. Objective absence of sweating is, however, significantly correlated, as expected, with increased skin resistance. Sweating tests also offer some confirmation of the observation noted above, that there is often an objective basis for the complaint of loss of sweating. 347

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