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Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries (1957)

Chapter: Neuropathological Predictions of Recovery

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Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
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Page 499
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 500
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 501
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 502
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 503
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 504
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 505
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 506
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 507
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 508
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 509
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 510
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 511
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 512
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 513
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 514
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 515
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 516
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 517
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 518
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 519
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 520
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 521
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 522
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 523
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 524
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 525
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 526
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 527
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 528
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 529
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 530
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 531
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 532
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 533
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 534
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 535
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 536
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 537
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 538
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 539
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 540
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 541
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 542
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 543
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 544
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 545
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 546
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 547
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 548
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 549
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 550
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 551
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 552
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 553
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 554
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 555
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 556
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 557
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 558
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 559
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 560
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 561
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 562
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 563
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 564
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 565
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 566
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 567
Suggested Citation:"Neuropathological Predictions of Recovery." National Research Council. 1957. Peripheral Nerve Regeneration: A Follow-Up Study of 3,656 World War II Injuries. Washington, DC: The National Academies Press. doi: 10.17226/18485.
×
Page 568

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Chapter XI NEUROPATHOLOGICAL PREDICTIONS OF RECOVERY William R. Lyons and Barnes Woodhall A. INTRODUCTION Collaborative histopathological studies on peripheral nerve injuries were begun by the present authors in 1944 at Walter Reed General Hospital with a number of objectives: (1) to obtain and record the histopathology in a well-studied, representative series of human peripheral nerve injuries treated by suture; (2) to forecast regeneration on the basis of careful histopathological study of the mirror images of the sutured ends and to correlate these forecasts with eventual clinical recovery; (3) to provide the surgeon with a pathologist's advice as an aid in achieving good nerve ends preparatory to suture; and (4) to make a histopathologic study of human nerve degeneration and regeneration and to develop a photographic record of these changes. Surgical decision was implemented by gross and his- tologic reports on over 600 lesions; the first and fourth objectives were largely attained with the publication of the Atlas of Peripheral Nerve Injuries (46) to which reference may be made for a technical discussion of histologic method; the second objective defines the scope of the present chapter. Many factors are thought to influence peripheral nerve regeneration; the neuropathologist was asked to make an intensive study of one of them, the surfaces joined by the surgeon in his definitive repair, with the assurance that there would be available for correlation studies not only clinical evaluations of eventual recovery but in addition such other details of the injury and its management as might also have an influence upon end- results. Since the pathological specimens were necessarily obtained at the time of suture, and by that tokt n independently of the clinical assessments of recovery 5 years later, it was not difficult to isolate the neuropathologist from all but the very earliest follow-up data and thus to preserve the integrity of his independent predictions based on the appearance of the nerve ends. Furthermore, since correlation studies could proceed only 499

after follow-up information had been obtained, it was natural to place in the hands of a disinterested third party, the statistician for the follow-up study, the actual task of correlation. In providing the surgeon with assist- ance at the time of repair, of course, the neuropathologist did obtain information on the nature and extent of the injury and on the details of management, together with a modicum of data on the early postoperative picture, but he made a conscientious effort to avoid being influenced by this information and to base his evaluations solely on the specimens and the slides. It was anticipated that any independent, predictive information which the neuropathological studies might contribute could easily be combined with similar information provided by other variables so as to make the best predictions possible as well as to determine the relative contributions of the various predictive variables. At the time the sampling plan for the follow-up study was crystallized, it may be recalled from chapter I, a special effort was made to allocate to the follow-up centers an appreciable number of men on whom histologic studies had been made. The entire roster (AFIP Accession No. 110,822) was used in this process, and at the conclusion of the study it was found that, of the 2,554 men used in the main statistical analysis, 356 had been allocated from the roster with histologic studies. Of the 356 men, 253, or 71 percent, were examined. In some of the latter group histologic studies were incomplete, the lesions were treated by neurolysis, partial suture, or graft, or a second suture had been necessary for which no histologic material was available. After all such cases were deleted there remained for study 181 complete sutures on the 7 major nerves, and these furnish the material for the present chapter. Table 243 contains for reference a listing of each case giving most, but by no means all, of the individual characteristics analyzed here. The 26 among them which are discussed in the Atlas (46) are cross-referenced to the latter by page. 500

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Code Equivalents for Table 243 Type of Injury to Nerve CD Complete nerve division PD Partial nerve division NC Neuroma in continuity Site of Injury to Nerve 1 Upper third of arm or thigh 2 Middle third of arm or thigh 3 Lower third of arm or thigh 4 Upper third of forearm or leg 5 Middle third of forearm or leg 6 Lower third of forearm or leg 7 Elbow or knee 8 Wrist or ankle 9 Hand or foot Injury to Operation, Tens of Days Days elapsing between injury and definitive suture were coded in 10-day intervale, so that 0 means 0 to 9 days, 1 means 10 to 19, 22 means 220 to 229, etc. Surgical Gap. cm. The surgical defect at the definitive suture was coded to the nearest cm., so that 01 means an interval from 0.5 to 1.4 cm., etc. Sensory Recovery Pain Threshold in Crams Numerical values—threshold as measured; only values of 40, 30, 20* 10, 6, and <6 gm. were employed. O No sensation D Deep pressure only H Hypesthesia, unmeasured V Unknown Touch Threshold in Grams Numerical values—threshold as measured; only values of 50, 35, 25, 16, 3, and <^3 gm. were employed. O No sensation or threshold <50 gm. H Hypalgesia, unmeasured V Unknown British Summary 0 Absence of sensibility in autonomous zone (AZ) 1 Recovery of deep cutaneous pain in the AZ 2 Recovery of superficial pain sensibility 3 Return of superficial cutaneous pain and touch throughout the AZ 4 Return of superficial pain and touch throughout AZ plus overreaction and inability to localize 5 Same as category 4 without overresponse 6 5 plus some two-point discrimination 7 Complete recovery V Unknown, not tested For a discussion of this code see chapter V, pp. 254-259. 510

Skin Resistance (SR) TA Elevated SR in total area AZ Elevated SR in autonomous area D Decreased SR N Normal SR M Mixed SR patterns V SR not tested, or otherwise unknown Motor Recovery Muscle Movements Separately for the proximal and distal muscles as defined in table 48, chapter III, all the muscles in the standard set are coded as to response to voluntary stimulation, as follows: 0 Not affected 1 No contraction 2 Perceptible movement only 3 Movement but not against gravity 4 Movement against gravity, but not against resistance 5 Movement against resistance X Affected, not tested V Unknown if affected However many muscles there may be in the standard set (for proximal or distal), the entry consists of a listing of the codes for each. The order of the listing is not anatomic but rather is that of the code. Thus an entry "1, 1, 1" means that all three standard muscles were affected and in none of them was contraction observed. An entry "0, 1, X" would mean that one of three standard muscles was not affected, another was affected but did not respond at all, and a third was affected but not tested. It will be noted in table 48, chapter III, that the abductor pollicis brevis was not a standard median muscle in the original protocol, but that use has been made of it in many cases. When the table gives two distal muscles the abductor pollicis brevis is included. When only one is given it is the opponens. British Summary 0 No contraction 1 Return of perceptible contraction in proximal muscles 2 Proximal muscles acting against gravity, no return of power in intrinsic muscles 3 Proximal muscles acting against gravity, perceptible contraction in intrinsic muscles 4 Return of function in both proximal and distal muscles so that all important muscles can act against resistance 5 Same as category 4-plus synergic and isolated movements 6 Complete recovery V Unknown For a discussion of this code, see chapter III, pp. 74—76. Practical Function Percentage of useful or effective recovery not only because of nerve and muscle recovery but also because of prosthetic devices, orthopedic procedures, etc. See chapter VIII for criteria. Pathologic Forecast See text, this chapter. It is the summary index only which is shown here. 511

B. METHODOLOGY The chief methodological problem concerns the choice of the character- istics considered to be descriptive of the lesion or, more specifically, of the surfaces joined by the surgeon. To the extent that the choice employed here is arbitrary, others might conceivably prove more fruitful. Both the distal and the proximal surfaces were evaluated, and four separate assess- ments were made for each in the form of expected percentage losses in recovery. The losses were estimated from the degree of fibrous or neuro- matous change evident in the (1) epineural, (2) interfascicular, (3) perineural, and (4) intrafascicular regions. There were thus 8 separate assessments, 4 for each nerve stump. The neuropathologist interpreted his task to be that of predicting regeneration across the gap and no farther; he paid no attention to other factors which must surely affect end results, e. g., the distance (or time) over which regenerating fibers must grow to reach their end-organs. To have incorporated into a single index estimates of the influence of additional variables would have made his ratings even more subjective than they necessarily were, and seemed unnecessary as long as there was every expectation that the effects of other variables could be controlled statistically. The decision was made to base the neuro- pathological ratings upon fibrosis generally rather than to make separate forecasts for the fine fibres (pain and autonomic) and the larger ones (pressure, touch, and motor). In reviewing the slides it often seemed that the fine fibres should get through without much trouble, whereas if the larger ones were capable of getting through they might not myelinate normally. The estimated losses, however, are not specific to one variety of fibre or another, but represent degrees of fibrous or neuromatous change, and may not apply with equal force to all varieties of fibers. Three more summary assessments were then derived from these on the following assumptions: 1. That the four icparate estimates for each nerve segment were independent and additive; and 2. That the condition of each nerve end was independent of that of the other, and nerve regeneration best viewed as a product of the residual chances of recovery obtained for each. Accordingly, the sum of the losses for each nerve stump was taken as a summary of the deleterious influences inherent in the condition of that particular nerve end. For each nerve end the complement of the losses was then obtained, i. e., the residual expectation of regeneration. Thus, if a poor distal end was assessed with deductions of 5,10,10, and 40 percent, or 65 percent in the aggregate, its expectation of regeneration was taken at 35 percent or .35. The separate expectations of the 2 nerve ends were then combined by multiplication; a distal nerve end rated at .35 and a proximal rated as .80 thus yielded an overall expectation of .28 (or 28 percent) for the recovery of the nerve. Especially arbitrary are the 3 summary assessments derived from the basic 8 enumerated above. The assumptions upon which they proceed are not 512

necessarily the best; the individual losses might not be additive, or, if additive, might better be weighted in some other fashion. The method of combining the assessments on the two nerve ends is obviously but one of several possible methods. If fibrotic areas are seen in both nerve ends and are so placed as to overlap considerably when joined together, the multi- plication procedure may exaggerate the effect upon regeneration. In general, however, since several cm. of nerve length were resected or obliterated by injury, the assumption that the nerve ends actually joined are independent of one another seems reasonable. Before the statistical analysis was begun, therefore, it was agreed that these 3 summary ratings might not provide the best combinations of the 8 unitary assessments and that, should any of the correlations prove at all promising, statistical methods would be employed to develop an optimum pattern for combining the 8 values. As it turned out, however, the correlations were not suffi- ciently encouraging to warrant the effort which such an analysis might have required. The process of classification is best explained on the basis of concrete examples, of which two sets are presented. The first, consisting of 9 illustrated cases, is drawn from those with follow-up information studied here but is probably also typical of the entire series of over 600 nerves. The second, consisting of 8 cases (including 1 in the first set of 9), was chosen to explain why so much emphasis has been placed on the appearance of the intrafascicular regions. The nine representative cases follow. Case 1193. A neuroma in continuity of the sciatic nerve in the middle-third of the thigh. The segment shown in plate 1 was removed and the nerve sutured 6% months after injury. Pathology. Proximal (plate 2) and distal segments (plate 3) were rated as in table 244. Deductions were made for slight fibrosis throughout the prox- imal stump, and for moderate fibrosis of the perineural and intrafascicular areas of the distal stump. The 10 and 25 percent estimated losses for the 2 nerve ends were combined into a summary estimate of recovery of 68 percent.27 Table 244.—.Neuropathological Ratings, Case 1193 Estimated percentage loss, by region evaluated Nerve segment Epi- neural Intcr- fascicular Peri- neural Intra- fascicular Total segment Proximal 2 0 5 0 3 0 15 10 25 Distal 10 Summary Index 68 "The complements of 10 and 25 percent, i. e., 90 and 75 percent, were multiplied to give the summary estimate of 68 percent. 4031)30—57- -35 513

Plate 1. Case 1193 Plate 2. Case 1193 Plate 3. Case 1193 Result. Pain thresholds 40 gm. in p. tibial and <6 gm. in c. peroneal; touch nil; autonomic good in both; motor good in peroneal, and fair in p. tibial proximal muscles, nil in intrinsic muscles. Complaints: some loss of gross muscle power, easy fatigability, excessive sweating, split sensation. Comment. The nerve cross sections were good and the recovery was good for a midthigh sciatic lesion. The explanation for some of the failure (e. g., touch) in this nerve may best be sought in the mismatched fasdcular pat- terns. The sciatic nerve at this level may have as many as 80 fascicles, and 514

when a long segment is removed the fascicular patterns of the ends finally sutured are usually entirely dissimilar. To illustrate this point as Sunder- land (78) has done, the fascicles of the distal section have been superimposed as rings on the proximal section. Even where a proximal fascicle or a frac- tion of one might happen to fall within any or all of the area of a distal one, it would be purely fortuitous that they should be the appropriate mates. Time fibrosis within the tubules of such a long distal segment might also help to explain why large fibers subserving touch and skeletal motor func- tions did not return adequately. One would also expect atrophy of the distal muscles. Case 3046. A complete severance of the posterior tibial nerve in the middle-third of the leg. The segments shown in plate 4 were resected and the nerve sutured 3 months after injury. Pathology. Proximal (plate 5) and distal (plate 6) cross sections were rated as in table 245. The small deductions for slight fibrosis in the epineural, interfascicular, and intrafascicular regions of both ends left a final rating of 68 percent. Result. Threshold for pain, 6 gm.; for touch, 16 gm.; autonomic good. Motor: 1 proximal and 2 distal muscles were tested and all contracted against resistance. Complaints: paresthesia, pain on use or pressure, bizarre sensory pattern (split sensation), adverse reaction to heat and cold. Plate 4. Case 3046 Plate 5. Case 3046 515

Plate 6. Case 3046 Comment. This case illustrates the aim of the surgical pathology team: to insure good nerve regeneration by resecting to the best possible cross sections proximally and distally. This was one of the more favorable cases in that only about 25 mm. had to be excised from each stump in order to eliminate most of the neuromatous and fibrotic tissue. On review, the pathology rating of 68 percent seemed somewhat severe and the correspondence between the nerve ends and functional return was good. Table 245.—Xeuropathological Ratings, Case 3046 Estimated percentage loss, by reqion evaluated Nerve segment Epi- neural Inter- fascicular Peri- neural Intra- fascicular Total segment Proximal 5 5 10 5 0 0 5 5 20 15 Distal Summary index 68 Imperfect matching of sensory fascicles rather than the slight fibrosis seemed the better explanation for pain and touch returns being subnormal. However, as may be seen in plates 5 and 6 the proximal and distal fascicular appositions were probably better than usual. Plate 5 shows the proximal cross section with the distal stump fascicles superimposed as inked-in rings. Epineural stitching would probably have brought about better conformity of these ends; and therefore might have permitted better fascicular apposi- tion than shown here. Only four of the proximal fascicles do not overlie some part of one or more of the distal rings. Two of the latter are not covered by some part of a proximal fascicle; but in these cases there are perineural contacts. 516

Case 3307. A double neuroma in continuity of the peroneal component of the sciatic nerve in the upper-third of the thigh. The 7 cm. specimen (plate 7) was resected and the nerve sutured 6 months after injury. An intraneural tantalum sling stitch was used. Pathology. Proximal (plate 8) and distal (plate 9) ends were rated as in table 246. The small deductions were made from both ends because of the mild degree of epineural and intrafascicular fibrosis shown in these plates, and the endoneural fibrosis (not visible at this magnification) that had developed in the 6-month interval. The final rating was 69 percent. Table 246. A'europathological Ratings, Case 3307 Estimate d percent; ige loss, b y region c valuatcd Nerve segment Epi- neural Inter- fascicular Peri- neural Intra- fascicular Total segment % 0 Proximal 5 5 0 10 Distal 5 5 3 10 23 Summary index 69 Result. Pain was elicited on deep pressure only; touch was nil; autonomic was poor in autonomous zone but normal in overlap areas; motor was nil in four muscles tested. Complaints: gross sensory and motor loss. Comment. Reasons for a nerve faring badly in spite of favorable histology in its sutured stumps have been dealt with extensively in other chapters. Some of these are: badly placed sutures or wrappers; a pathologic "bed"; high lesions resulting in postoperative "time" fibrosis in the distal tubules; stretch fibrosis because of the necessity of resecting too extensively; asso- ciated bone, vascular, or other nerve lesions; mismatched proximal and distal fascicular patterns such as illustrated in plate 8 in which the inked-in rings represent the distal fascicles in one possible pattern of apposition with the underlying proximal fascicles. In this case the double neuroma neces- sitated a long resection; and the surgeon felt that a sling suture was neces- sary because of tension. This precaution against separation at the suture line—notoriously frequent in this nerve—must have seemed the lesser of two evils, the other being the likely stretch fibrosis known to occur in such Plate 7. Case 3307 517

Plate 8. Case 3307 Plate 9. Case 3307 cases when the knee was eventually extended. Although this nerve was not considered to have separated, the functional return was consistent with that of a disrupted nerve or one that had undergone stretch fibrosis. Pain was elicited with deep pressure in the autonomous zone; but this may have been due to an overlapping nerve in the sclerotomal regions. Case 3197. A completely severed sciatic nerve in the middle-third of the thigh. Segments shown in plate 10 were resected and nerve was sutured 10K months after injury. Pathology. The specific ratings were as in table 247. The summary rating was poor (21 percent) not only because of the neuromatous proximal stump, but because of the shrunken fibrotic distal fascicles (plates 10, 11, 518

and 12). It is clearly shown in these plates that the cross-sectional fascicular and tubular areas are reduced to a small fraction of the normal with replace- ment by fibrous and adipose tissue. Result. Pain threshold 40 grn. and touch 25 gm. for both nerve components; autonoir.ic was poor. Six of the 8 tested proximal muscles showed varying Table 247.—Xeuropathological Ratings, Case 3197 Estimated percentage loss* by region evaluated Nerve segment Epi- Inter- neural fascicular Peii- ncural Intra- fascicular Total segment 5 0 15 5 5 10 15 40 65 Distal i 50 21 . Plate 10. Case 3197 519

Plate 12. Case 3197 degrees of functional return but with only 1 muscle for each nerve con- tracting against resistance; complete paralysis of the intrinsic muscles. Complaints: paresthesia, gross sensory loss, pain on use or pressure, some loss of gross muscle power, adverse reaction to heat and cold, loss of sweat- ing, split sensation. Comment. Upon reviewing this case in face of the follow-up evidence, the distal tubules were still considered to be very fibrotic and unfavorable for good expansion of thick, myelinated axons. At the time of the original microscopic examination it seemed reasonable to predict that amyelinated axons might progress along the lines of Schwann cells shown in the shrunken tubules (plate 12) and that if full myelination were not a prerequisite to function, such axons might indeed subserve their normal function. One usually expected that pain and autonomic fibers might regrow and function under spatial circumstances thought to be inadequate for voluntary effectors* touch, pressure, and muscle sense receptors. There remains the possibility that regeneration and maturation might have taken place in the extensive interfascicular regions, which, in this nerve, consisted of well-vascularized adipose and loose areolar tissue. Nerve fibers do proliferate in extra fascicular areas; but whether these regions provided the growth facilities in the nerve in question or merely permitted expansion of the contracted reinnervated tubules remains unknown. Case 4472. A completely severed ulnar nerve in the middle-third of the arm. Nerve ends were coapted at the time of injury. Definitive suture was performed after resection of specimen shown in plate 13 8% months later. Pathology. Small deductions were made because of slight fibrosis in epi- neural and interfascicular regions in both proximal (plate 14) and distal (plate 15) sections, and slight perineural fibrosis in the distal fascicles; the specific deductions were as in table 248. The large deduction was made from the distal section because of the endoneural fibrosing process that had almost obliterated the neurilemmal tubules. The summary rating was 19 percent. 520

Plate 1 3. Case 4472 •f Plate 14. Plate 15. Case 4472 521

Table 248.—Neuropathological Ratings, Case 4472 Estimate d percent; ige loss, b y region e valuated Nerve segment Epi- neural Inter- fascicular Peri- neural Intra- Total segment fii-iiic-ul.il- Proximal 2 3 0 0 5 Distal 5 10 5 60 80 Summary index 19 Result. Pain threshold 6 gm., and touch 25 gm.; autonomic was poor in the autonomous zone and normal in the overlap areas; of the 2 proximal and 3 distal muscles tested, all contracted against resistance. Complaints: spontaneous pain, pain on use of hand, feeling of coldness, adverse reaction to heat and cold, gross sensory loss, some loss of fine muscular coordination* easy fatigability, incomplete opposition. Comment. This case proved interesting because the nerve ends were rated as fair at surgery, but, after microscopic examination, the degree of intra- fascicular "time" fibrosis influenced the judgment of the pathologist to such an extent that one of the lowest ratings in the series was finally given to this nerve. This is another of several examples encountered in this survey indi- cating that voluntary motor fibers may regenerate along fibrotic fascicles and reactivate the denervated muscles. That normalcy was not attained in this patient may be deduced from the number of complaints listed above. Case 3269. An ulnar nerve completely severed in the middle-third of the forearm; bulb-sutured 3Jj months after injury, and definitively sutured 2J; months later after resection of the suture-zone neuroma (plate 16). Pathology. Proximal (plate 17) and distal (plate 18) segments were rated as in table 249. The distal end was one of the worst seen in this series due in part to a stretch fibrosis apparently induced by the bulb suture. The summary rating was 26 percent. Result. Pain threshold 10 gm. and touch 16 gm.; autonomic return was equivocal, a mixed skin resistance pattern having been coded; proximal muscles not involved but 2 of the 3 distal muscles tested contracted against resistance, the other against gravity. Complaints: paresthesia, gross sensory loss, some loss of fine muscular coordination, split sensation, brace used. Plate 16. Case 3269 522

Plate 17. Case 3269 Plate 1 8. Case 3269 523

Table 249.—.Vmropathological Ratings, Case 3269 Estimate d percent. ige loss, by region e valuated Nerve segment Epi- neural Inter- fascicular Peri- Intra- neural fascicular Total segment Proximal 5 5 3 0 13 Distal 10 25 0 35 70 26 Comment. The result might be rated as fair, and even this seemed incredible* in view of the distal cross section. The pathologist recorded the presence of about 10 shrunken distal fascicles among fibrotic surroundings, and also noted that amyelinated axons had grown into some of them following the bulb suture. In order to qualify the record of this unexpected functional recovery, some of the adverse phenomena coded under complaints (see above) must receive due consideration. Case 5357. A severed posterior tibial nerve, the stumps of which had remained in fibrous continuity. Severance point was in the middle-third of the leg. Resection of 2 segments, together measuring 6 cm. (plate 19) was done, and neurorrhaphy performed 11 months after injury. Pathology. The proximal (plate 20) and distal (plate 21) cross sections appeared grossly good, but on microscopic examination the distal fascicles Plate 19. Case 5337 V. ' vv. * Plate 20. Case 5357 524

Plate 21. CW 5557 showed extremely shrunken tubules, and endcneural fibrosis to a degree comparable to that shown in plate 37. The specific ratings appear in table 250. The summary rating of 11 percent was one of the lowest in the series. Table 250. -.\europathological Ratings, Case 5357 Estimated percentage loss, by region evaluated Nerve segment Epi- ncural Inter- fascicular Peri- neural Intra- fascicular Total segment 0 3 5 10 2 5 0 70 7 88 Distal . . . Summary index 11 Results. Pain threshold 30 gm.; touch 3 gm.; autonomic was normal; of 5 muscles tested, 4 (proximal) contracted against resistance, and 1 (distal) contracted, but not against gravity. Complaints: paresthesia, gross sensory deficit, loss of fine muscular coordination, easy fatigability, stiff joint, adverse reaction to heat and cold. Comment. In plate 21 the inked-in circles represent the proximal fascicles in a way that may be said to approximate their relation to the distal fascicles at suture. Of 20 large and small proximal fascicles, 5 show no contact whatso- ever with distal fascicles. Even with overlap there can be no assurance that the proximal fascicle overlies its distal mate. On the other hand, propin- quity of proximal and distal mates may permit regenerating axons to reach their normal endings since, at the point of surgical severance, there is always a tendency for single axons to send out many branches, sometimes as many as 50, along paths of least resistance. This case is presented for another reason. Although the recovery was greatly in excess of what was expected from microscopic examination, it is necessary to discount the credit for proximal muscle recovery. The lesion was in midleg and not all the branches to the proximal muscles would, therefore, be involved. In fact, 525

the operative note specifically recorded contraction of gastrocnemius and soleus upon stimulation, muscles credited with 80 percent power. Case 1214. A severed ulnar nerve, middle-third of forearm; temporary suture at time of injury and 5}j months later the specimen shown in plate 22 was resected and neurorrhaphy performed. Pathology. The proximal (plate 23) and distal (plate 24) sections were rated as in table 251. The summary rating was 71 percent. Result. Pain threshold 20 gm. and touch 16 gm.; autonomic was normal; of 3 distal muscles affected, 2 were tested and both contracted against resistance. Complaints: spontaneous pain, paresthesia, feeling of coldness, pain on use or pressure, some loss of gross muscle power, fatigability on long use. At the time of nerve injury the ulna and radius had been fractured, and there was a residual orthopedic deformity. Comment. This is an example of a case with better than usual nerve ends showing good although not perfect functional recovery. There was good practical function with an overall rating of 80 percent. Dynamometry on the 2 distal muscles showed 80 percent of normal. Failure of pain and touch fibers to return more abundantly to the autonomous zone may find Plate 22. Case 1211 Plate 23. Case 1214 526

Plate 24. Case 1214 an explanation in a possible mismatching of proximal and distal fascicles, as illustrated in plate 24. Here the proximal fascicles represented by the black circles are superimposed upon the distal cross section in one form of appositional pattern that may have resulted at suture. A few of the fascicles of each stump do not have corresponding mates, and even where there is some measure of matching, there is no way of knowing whether the suture brought the appropriate fascicles together. Table 251.—Neuropathological Ratings, Case 1214 Estimated percentage loss, by region evaluated Nerve segment Epi- neural Inter- fascicular Peri- neural Intra- fascicular Total segment 0 5 3 2 5 0 10 5 25 Distal 5 71 Case 3250. A neuroma in continuity of the ulnar nerve, and a complete severance of the radial nerve at the elbow. The specimens shown in plate 25 were removed and sutures performed 80 days after injury. Pathology. The ulnar ends (plate 25 upper), proximal (plate 26), and distal (plate 27) were rated as in table 252. The summary was 70 percent. The radial nerve (plate 25 lower), proximal (plate 28), and distal (plate 29) re- 527

ceived the deductions shown in table 253. The summary was 41 percent. The proximal nerve stump was split into two parts for suturing, the smaller being somewhat less fibrotic and neuromatous than the extremely poor larger division. Table 252.—Xeuropathotogical Ratings, Case 3250 (Ulnar) Estimated percentage loss, by region evaluated Nerve segment Epi- neural Inter- fascicular Peri- neural Intra- fascicular Total segment Proximal . . 5 3 5 2 3 0 10 13 20 Distal 5 Summary index 70 Table 253.—Neuropathologicd Ratings, Case 3250 (Radial) Estimated percentage loss, by region evaluated Nerve segment Epi- ncural Inter- fascicular Peri- neural Intra- fascicular Total segment Proximal 10 40 5 o 55 Distal 0 0 5 10 Summarv index 41 Plate 25. Case 3250 528

Result. Ulnar. Pain threshold 40 gm.; touch nil; autonomic was poor in the autonomous but normal in the overlap area; motor was fair, 4 of 5 tested proximal and distal muscles showing varying degrees of return, including 1 that contracted against resistance. V^kr ^•"™"^' Plate 26. Case 3250 Radial. Pain threshold 40 gm.; touch nil; autonomic was normal; motor was good, all of the 6 tested proximal and distal muscles contracting against gravity and 2 against further resistance. Complaints: paresthesia, some loss of fine muscular coordination, fatigability on long use, adverse reaction to heat and cold. Same for ulnar nerve. Comment. This case is presented because it afforded an opportunity to compare 2 nerves, 1 with a good rating and the other with a low rating, in the same patient. Although it is impossible to summate the functional returns for correlation with the pathology rating, it would seem safe to conclude that the result with the radial nerve, which had the poor ends, 4031130—57- -36 529

was as good if not better than that with the highly rated ulnar nerve. Although the ulnar nerve sections were good, the fascicular patterns varied considerably at the two ends of the resected neuroma, as shown in the illustrations. Apparently proximal fascicles that carried sensory and autonomic fibers supplying the autonomous zones were not in apposition with their distal mates. It is not difficult to understand how the neurom- atous radial proximal stump* largely motor at this level, sent some fibers down some of the rather widely separated distal fascicles to give the patient a fairly good return of wrist and finger extension, without good coordination of fine movements. Plate 27. Case 3250 Eight cases, illustrated in plates 30-37, have been chosen to exhibit variation in distal tubular diameters and to suggest their relation to the interval from injury to suture. All plates are cross sections of a representa- tive distal fascicle stained with protargol-analine blue, enlarged 600 times. 530

Plate 28. Case 3250 531

Plate 29. Case 3250 Case 3288 (plate 30). Complete severance, median n. upper-third of fore- arm; 13 days after injury. Neurilemmal tubules were widely "patent" and still contained degenerating axonal and sheath material and macrophages. The specific assessments are as in table 254. The summary rating was 83 percent. Recovery: pain threshold 6 gm.; touch 16 gm.; autonomic was poor in total area; 4 of 4 muscles tested showed good contraction. 532

Table 254.—Neuropathological Ratings, Case 3288 Estimated percentage loss, by region evaluated Nerve segment Epi- neural Inter- fascicular Peri- neural Intra- fascicular Total segment 3 3 2 5 0 0 0 5 5 13 Distal Summary index * . ... 83 Plate 30. Case 3288 Case 3233 (Plate 31). Neuroma in continuity, median n. mid-third of arm! 2 months after injury. Tubules were maximally distended, and a few amyelinated axons shown as minute black dots had grown through the neuroma and along the tubules. The specific assessments are as in table 255. The summary rating was 88 percent, the second highest in the entire series. Plate 31. Case 3233 533

Table 255.—Neuropathological Ratings, Case 3233 Estimated percentage loss, by region evaluated Nerve segment Epi- neural Inter- fascicular Peri- neural Intra- fascicular Total segment 5 2 0 0 0 0 7 5 Distal 0 5 88 Recovery: pain threshold 10 gm.; touch nil; autonomic was poor in autono- mous zone only; all five affected muscles showed good contraction. Case 3420 (Plate 32). Neuroma in continuity, sciatic n. upper-third of thigh; 3}j months after injury. Most of the tubules showed considerable shrinkage, this being typical of all areas of all fascicles. The individual deductions are as in table 256. The 25 percent deduction was made for shrinkage although the endoneurium was not dense, but rather a fine reticulum. Amyelinated axons had grown within and between the tubules. The summary rating was 49 percent. Recovery: pain felt on deep pressure only; touch nil; autonomic was poor in total area; of 7 muscles tested, 1 showed good contraction, 4 were weak, and 2 remained paralyzed. Table 256.—Neuropathological Ratings, Case 3420 Estimated percentage loss, by region evaluated Nerve segment Epi- neural Inter- fascicular Peri- neural Intra- fascicular Total segment Proximal 5 10 3 0 18 Distal 5 5 5 25 40 Summary index .... .. 49 Case 1177 (Plate 33). Neuroma in continuity, ulnar n. at elbow; 4 months after injury. Most of the tubules in all fascicles showed consider- able shrinkage—a few remained patent as shown. Fine axons had grown along the inside and outside of the tubules. About 10 of these may be seen around the periphery of the large tubules in the upper right corner. The deductions appear in table 257. The summary rating was 63 percent. Recovery: pain threshold 40 gm.; touch 16 gm.; autonomic was normal; all 3 of the 3 tested muscles contracted well. 534

Table 257.—.\europathological Ratings, Case 1177 Estimated percentage loss* by region evaluated Nerve segment Epi- neural Inter- fascicular Peri- neural Intra- fascicular Total segment Proximal . 3 3 5 5 2 2 0 20 10 30 Distal 63 Plate 32. Case 3420 Plate 33. Case 1177 Case 3405 (Plate 34). Complete severance, radial n. lower-third of arm; 4 months after injury. Most of the tubules showed diameters that were reduced in comparison with the 2-month case, but were about equal to those of case 3420 (3}s months). Even in this severed nerve a scattering of fine axons had found their way into the distal stump, a frequent finding. A deduction of 20 percent was made because of tubular shrinkage and beginning endoneural collagenization; other deductions are as shown in 535

table 258. The summary rating was 44 percent. Recovery: pain threshold 6 gm.; touch 25 gm.; autonomic was poor in the autonomous zone only: of the 7 muscles tested 2 contracted well and 5 poorly. Plate 34. Case 3405 Case 3342 (Plate 35). Neuroma in fibrous continuity, posterior tibial n. lower-third of leg; 5 months after injury. Most of the tubules in all of the distal fascicles appeared shrunken, although the endoneural fibrosLs was Table 258.—.\europathological Ratings, Case 3405 Nerve segment Estimated percentage loss, by region evaluated Epi- neural Inter- fascicular Peri- neural Intra- fascicular Total segment Proximal 5 5 10 0 20 Distal 10 10 5 20 45 44 Plate 35. Case 3342 536

not severe. A few amyelinated axons had penetrated the fibrous connection at the severance point and reached these distal tubules. Deductions were as shown in table 259. The summary rating was 44 percent. Recovery: pain felt on deep pressure only; touch threshold 50 gm.; autonomic was normal; the one muscle tested showed good contraction. Table 259.—.\europathological Ratings, Case 3342 Estimated percentage loss, by region evaluated Nerve segment Epi- neural Inter- fascicular Peri- neural Intra- fascicular Total segment Proximal 5 5 C 5 5 30 20 45 Distal 5 Summary index 44 Case 3268 (Plate 36). Complete severance, c. peroneal n. at the knee; 5% months after injury. All tubules showed shrinkage to fairly uniform diame- ters, approximating 10-15 micra. In the plate, they appear as closely packed ringlets of reticulum. The deductions were as shown in table 260. The summary rating was 45 percent. Recovery: no pain sensation felt; touch nil; autonomic was poor in the autonomous zone only; none of the four tested muscles contracted. Plate 36. Case 3268 Case 3197 (Plate 37). Sciatic nerve injury previously discussed on page 518. Neurilemmal tubules could be seen with difficulty because of shrinkage and fibrotic endoneurium. Deduction was 50 percent for the distal intra- fascicular area, and this plus further penalties for fibrosis in the other areas left a 21 percent rating. 537

Table 260.—.\europathological Ratings, Case 3268 Estimated percentage loss, by region evaluated Nerve segment 1 Epi- Inter- neural fascicular Peri- neural Intra- fascicular Total segment Proximal . . 1 5 0 10 0 30 10 50 Distal 5 Summary index. 45 Plate 37. Case 3197 The foregoing cases suggest that a surgeon may electively resect to ends presumably devoid of deleterious pathological changes* and nevertheless obtain a functional result far from perfect. The mismatching of one or two small fascicles may have prevented such cases as 3288 and 3233, for which the pathological picture is so favorable, from showing good sensory and autonomic recovery even though the muscle recovery was good. Such results are not predictable on the basis of pathologic study. At the opposite extreme are individuals like patient 3197 whose distal tubules presented so shrunken an appearance that the pathologist concluded the chance of regeneration was quite poor (21 percent), and probably confined to the small fibers. The observed result might indeed be classified as poor, but it would hardly be expected that a high sciatic lesion of severance, sutured 10)4 months after injury, with resection to fascicles already fibrotic and supposedly destined to become even more so, should show even the indi- cated degree of functional recovery. It would seem that axons need not be thick and well-myelinated to transmit tactile impulses and to activate skeletal muscles, or that such axons did indeed maturate fully in spite of the spacial limitations detected in the distal sections. 538

The sample cases also suggest the strong association between degree of fibrotic change and time from injury to suture, which is discussed in a subsequent section. The pathologist's forecasts were not made for each modality but represent overall judgments as to the chance of regeneration generally, whereas regeneration was assessed in terms of specific modalities. To the extent that recovery was generalized, as in the functional ratings, it stems from clinical concepts of useful function rather than from quantitative estimates of the number of axons reaching their appropriate end-organs. This discrepancy between the points of view from which the pathological and the clinical evaluations were made has not been thought, however, to interfere with their correlation in any way. Fibrotic and neuromatous changes are viewed as impeding the regeneration of each type of axon, and if there be differences in their effects upon the various types of axons these differences are viewed as essentially quantitative in nature. Thus an overall recovery forecast of 50 percent may mean one thing for pain fibers and quite another for touch, but in each instance should be associated with better recovery than a forecast of, say, 10 percent. Accordingly, so long as any pathological assessment or combination of assessments is studied in relation to a single modality, any effect should be a scalable one, whereas this may not be true if recovery is represented by a composite such as the British summary of sensory regeneration or the overall functional assessments. The content of the follow-up examination has been described and evalu- ated in previous chapters. In preparing the present chapter the writers had access to all the follow-up information coded by the several centers, but at a time well in advance of the preparation of final manuscripts on these chapters and, by that token, before the quality and full meaning of the data had been completely appraised. However, on the basis of what was known at the time and the specifications which the neuropathologist made for the statistical studies, the following selection was made from among the various elements of the follow-up examination: Pain threshold. Touch threshold. Skin resistance. British summary of motor recovery. Number of affected proximal muscles contracting voluntarily. Number of distal muscles contracting voluntarily. Overall functional evaluation. Strength of selected individual muscles. As an initial step in the exploration of the prognostic significance of the neuropathologic forecasts, individual and summary assessments were separately correlated with particular modalities of follow-up status to ascertain whether, regardless of the influence of other variables, the con- dition of the nerve ends seems to have an important bearing upon eventual recovery. These early tables were also useful in that they showed the summary forecast to be an adequate basis for all later work. Subsequently, better controlled studies were made by removing the influences of other 539

variables, e. g., time, length of surgical gap, etc., which in earlier analyses, especially that on motor recovery, had been thought to affect regeneration. The effects of such variables were removed by correlating pathological assessments and follow-up status within subsets of the sample so chosen as to be homogeneous with respect to such control variables. The amount of material is so small that only one control variable could be used at a time, as a rule, so long as only these simpler statistical devices were em- ployed. Although preparation had been made for more elaborate correla- tion studies, employing several predictive variables and several control variables simultaneously, the early results were considered not to justify an elaborate, multivariate analysis. The following eight variables were used as controls: Site of lesion. Presence of associated arterial lesion. Number of operations. Days from injury to definitive operation. Special operative features. Type of cuff. Use of stay suture. Length of surgical defect. Although correlation studies were done on the basis of individual nerves as much as possible, because the cases were so few it was necessary at many points to combine two or more nerves, especially in the lower extremity. The sample of 181 lesions finally used in the statistical studies is distributed as follows among the seven major nerves: Median 29 cases Ulnar 50 cases Radial 23 cases Peroneal 13 cases Tibial 17 cases Sciatic-peroneal 30 : Sciatic-tibial 19 . For purposes of tabulation the nerves were usually grouped as follows: Ufpfr Exlrtmily Median 29 cases Ulnar 50 cases Total, including radial 102 cases Lawn Extremity Peroneal plus sciatic-pcroneal 43 cases Tibial plus sciatic-tibial 36 cases Total lower extremity 79 cases Whenever a group of two or more nerves did not differ greatly as to level of recovery in a given modality, they were pooled for the particular corre- lation study contemplated. The various inflicting forces acted indiscrimi- nately upon all nerves, and the same readily recognized types of damage were created in all. Finally, the problem of correlation was approached in most general terms, with no particular emphasis upon the prediction of either especially 540

good or especially poor results at follow-up. In some instances, e. g., skin resistance, the follow-up information provides no more than a dichotomy, while in other instances functional return is scaled in some detail. In the latter the analysis has been oriented by the amount of information available and the nature of the distributions themselves and not by any emphasis on one or the other end of the recovery scale. C. GROSS VARIATION IN PATHOLOGICAL PREDICTIONS OF REGENERATION The pathological assessments for all nerves combined are shown in figure 23 for each variety of assessment, and the summary assessments in figure 24. The great majority of the individual estimates of percentage loss is below 10 percent for each assessment except for that on the intra- fascicular region of the distal segment, for which 90 percent lie above this point. As would be expected from the top panels of figure 23, the aggre- gate estimate of loss for the proximal segment is usually below 20 percent. For the distal segment, on the other hand, the aggregate loss is usually above 20 percent, and the evaluation of both segments reflects very largely any estimated losses attributed to the appearance of the distal segment. The individual cases summarized above exemplify the way in which the specific assessments are combined to produce the summary assessments, and further illustrate how critical is the estimated loss in recovery attributable to the intrafascicular region of the distal segment: it is the chief ingredient of the overall summary based on the appearance of both ends. Variation among nerves is greater than one would expect from purely random variation. Table 261 contains the mean values of the summary estimate of regeneration. Several comparisons were made, with the following results: All nerves <.01 Upper v. lower <.01 Median v. ulnar v. radial > -05 Sciatic-peroneal v. sciatic-tibial >.05 Peroneal v. tibial >.05 Sciatic-peroneal v. peroneal. . . ^.OS) o . . ... , .. * C «c fcombmed P>.05 Sciatic-tibial v. tibial >.051 The differences are in line with any expectation based on functional re- covery: they are less extensive than might be anticipated from observed variation in motor recovery. One would expect war wounds affecting peripheral nerves to be quite variable from lesion to lesion, but not, in the aggregate, from nerve to nerve, and it is of some interest that the patho- logical assessments serve to distinguish the individual nerves at all. In chapter II it was noted that the nerves differ somewhat as to characteristic interval from injury to definitive suture, ulnar and radial lesions being operated upon earlier than the others, and median, peroneal, and tibial later. Plainly the pattern of variation among nerves is not the same in 541

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Figure 24. Percentage Distributions of All Lesions by Summary Pathologic Ratings ftKtt OF C H.Att pERC ENTAGE CASES 100 100 ASES OF PROXIMAL 80 80 60 40 20 60 40 HI 0 )0 0 20 40 60 80 1C PERCENTAGE LOSS IN EXPECTED REGENERATION 100 80 60 100 80 60 DISTAL . 40 20 0 40 20 pJSSB^^Rl 1 1 llilsWSl . If •'••'••'••'••• -: 1 _t ...c t |.x-x -••-:-;•-•.•{•.•.•:•:•:•.•.•. ••:•:!:•:- -.-"-: :•••.•. -[:. ;-;•: \ \ • •.:•.-.:•. .\.-:-y.-:-:-:-r t :-:•:•:!;:-.-: :-:-:-:-: : .-*:•.-::-.-.•:•.•:•>: 0 X) 100 J 20 4O 60 80 1( PERCENTAGE LOSS IN EXPECTED REGENERATION 100 80 80 BOTH ENDS 60 40 20 O 60 40 20 0 20 40 60 80 PERCENTAGE RECOVERY FORECAST 100 543

the pathologist's ratings as it is in the distributions on interval from injury to definitive suture. Table 261.—Mean Summary Forecast of Percentage Chance of Regeneration, by Xerve Nerve Number of lesions Mean forecast Median 29 59 24 Radial 23 51. 70 Ulnar 50 51.60 13 43 54 Sciatic-peroneal . . 30 39. 57 Tibial 17 49. 12 Sciatic-tibial 19 41 68 Since fibrotic and neuromatous changes are initiated by injury, and take place gradually thereafter, their extent at the time of repair should be somewhat correlated with the length of the interval from injury to suture. One would expect, therefore, that the neuropathologist's estimates of the effect of such changes upon regeneration would be similarly correlated with the preoperative interval. Since the neuropathologist read fibrosis as he saw it, without reference to the time interval, it is instructive to study his assessments in relation to time, as may be done from table 262, which represents the overall pattern of variation for all nerves combined. The fact of association between time and pathological rating is quite reliable in the statistical sense, but in degree unimpressive. However, the values for cases grouped by nerve fall in among these mean values somewhat in re- lation to time and there remains some possibility that the association reflects merely some variation among nerves. The material was retabulated, therefore, to show the correlation between the two variables in detail, and by nerve. The correlation diagrams suggested that linear correlation coefficients were appropriate. For all nerves combined the coefficient is — .40 on 181 cases and the equation of best fit Y=62.52—.081X where Y is the forecast and X time from injury to surgery in days. A difference of 100 days in the interval, that is, would change the forecast by 8.1 units. Inspection of the correlation diagrams for the individual nerves suggested that approximately the same relationship holds for each nerve. Accordingly, calculations were carried out for only the ulnar which has the only large group of cases. The correlation coefficient for the 50 ulnar in- juries was found to be —.41, and the best-fitting straight line Y=78.35-.105X 544

In short, the observed association does not merely reflect some variation among nerves but is characteristic of individual nerves. Table 262.—Summary Forecast of Regeneration by Days From Injury to Definitive Suture, All Nerves Combined Forecast (percent) Days from injury to suture 0-109 110-169 170 or more Total 03-07 1 0 0 1 0 3 4 5 1 11 12 4 4 19 7 5 3 0 0 2 7 1 4 7 4 3 2 8 5 2 2 3 6 0 0 0 0 3 8 3 5 11 10 11 5 22 23 11 10 24 21 6 5 1 2 08-12 ... 1 1 1 13-17 18-22 23-27 1 2 3 2 3 6 5 4 2 8 1 2 1 2 28-32 33-37 . . 38-42 43-47 48-52 53-57 58-62 63-67 . 68-72 73-77 78-82 83-87 88-92 Total 46 79 56 181 53.5 54.7 37.7 49.1 Correlation ratio: —.39; P<.01 Time also plays a role after suture, for the axons require time to grow down the empty distal tubules and to forestall any further intrafascicular or tubular fibrosis. If preoperative time is of significance in influencing distal tubular fibrosis, equal consideration should be given to the postoperative period in which tubules are empty and presumably shrinking. It might be expected that preoperative changes would be reflected in the neuropatholo- gist's assessments, but the only measure of postoperative change is provided by the height of the lesion or, more precisely, the distance from lesion to end-organ. High lesions operated upon long after injury will, on this analysis, fare badly. Further, one would not expect the neuropathologist's assessments to vary by site, and indeed this is the case, as may be seen in table 263. The high-low differences evident there are obviously within the range of chance variation, although formal tests have not been done. 403930—6*7- -87 545

Since height of lesion is associated with degree of clinical recovery, but does not affect the neuropathologic forecast, one would expect that a control on site would be especially important in correlation tables on recovery versus forecast. Table 263.—Mean Summary Forecast of Regeneration and Gross Site of Lesion, by Nerve Nerve Hif ;h' Lo IT I Number of lesions Mean forecast Number of lesions Mean forecast Upper extremity Median 12 62.25 17 57. 12 Ulnar 19 53 74 29 51.41 Radial 18 53 27 2 52.07 Total 49 55.65 48 53.46 Lower extremity Peroneal and sciatic-peroneal . 32 39.72 11 43.82 Tibial and sciatic-tibial 19 41.05 15 47.53 Total 51 40.22 26 45.96 1 As used in earlier chapters; in the upper extremity high lesions are those on the arm or at the elbow, and in the lower extremity on the thigh or at the knee. Length of surgical gap is another fundamental characteristic of the nerve lesion as finally sutured. It was shown above (p. 154) that length of gap and interval from injury to suture are reliably correlated, presumably be- cause the surgeon finds more fibrosis after a long interval and tends to resect farther. On this basis, one would expect some association between gap and pathologic forecast. Of course it must also be borne in mind that the length of nerve resected by the surgeon in attempting to remove pathologic tissue represents an interaction of opposing influences, since his purpose is to achieve good ends provided the gap thus created can still be closed by suture. In general, and within limits, the farther back the surgeon resects the better will be the ends he finally brings together, but the farther back he finds it necessary to resect the more fibrosis there was in the first place. In table 264 appears a summary of the association between length of surgical gap and the summary forecast; the association is much like that between time and pathologic forecast. Some refinement would be intro- duced by separate analyses by nerve, since the various nerves are by no means uniform as to length of gap, but for none of the individual nerves is the association between forecast and length of gap a very intimate one.

Finally, as noted in the motor chapter (p. 170) there is a strong correlation between the operator's gross evaluation of nerve ends prior to anastomosis and the neuropathologic forecast of expected regeneration. Table 264.—Summary Forecast of Regeneration, by Length of Surgical Gap at Definitive Suture, All Nerves Combined Forecast (percent) Surgical gap, in cm. 0-4.4 4.5-6.4 6.5 or more Total 03-07 1 1 1 0 1 3 2 0 9 3 1 2 7 5 1 3 1 2 0 2 0 2 0 1 1 3 7 10 6 6 7 8 4 2 0 0 2 5 1 3 10 6 8 2 5 10 4 2 10 6 0 0 0 0 3 8 2 5 11 10 11 5 21 23 11 10 24 19 5 5 1 2 08-12 13-17 18-22 23-27 . 28-32 33-37 . . . 38-42 43-47 48-52 53-57 . . . 58-62 ... 63-67 68-72 73-77 78-82 83-87 . . 88-92 Total 43 59 74 176 54.2 54.7 41.4 49.0 Correlation ratio: —.33; P<.01 D. CORRELATION BETWEEN NEUROPATHOLOGICAL FORECASTS OF REGENERATION AND CLINICAL ASSESSMENTS OF EVENTUAL RECOVERY As might be anticipated from the distributions in figures 23 and 24, when preliminary tables were prepared to explore the individual and summary assessments prepared by the neuropathologist, it was found that three assessments gave essentially the same information: intrafascicular region of distal segment, entire distal segment, and both segments combined. However, since the variation associated with the summary forecast seemed slightly greater than with the other two, it was chosen to represent the neuropathologic evaluations in the correlation studies which follow. Each modality of the clinical follow-up examination is discussed in a 547

separate section, first without regard to other such variables and then with regard to such variables as seemed, in the earlier chapters, to influence eventual recovery. 1. Pain Threshold In the chapter on sensory regeneration it was shown that the determina - tions of pain thresholds varied less among the several centers than any other test of sensory recovery, and it was concluded that the clinical evaluation of pain threshold is the most reliable of the sensory indices. Table 265 provides the basic information on the relation between pain threshold and summary forecast of expected regeneration. Although the grouping of sciatic-peroneal with peroneal and sciatic-tibial with tibia I may obscure slightly the association between the regeneration forecast and final level of pain sensibility, it would appear from table 265 that any association is at best quite weak. From the analysis of possible determinants of pain recovery presented in chapter V, in which so few variables appeared to have a significant influence upon pain threshold at follow-up, and none to have a really important influence, it would not be expected that the introduction of any third variable as a control would materially improve the association revealed in table 265, and such proved to be the case. Table 266 summarizes the results obtained with several which seemed, on inspection, to improve the association slightly; such improvement may be within the bounds of chance. The 4 control variables employed in table 266 merely provide different ways of regrouping the material, and some of the control variables them- selves are closely associated. For example, in the upper extremity low lesions tend to be those without associated arterial injury. Table 267 has been prepared to show just how close the relationship is between forecast and pain threshold under favorable circumstances. From table 266 were chosen those controlled comparisons in which the association seemed closest, i. e. Median—without associated arterial injury Ulnar—below elbow All four lower extremity nerves combined—cuff used For each of these table 267 shows in somewhat more detail the association between forecast and pain threshold. Although the selection of the tables has been such as to favor the relationship, even on these terms it does not appear to furnish the basis for reliable clinical predictions. No numerical measure of the relationship seems useful. 2. Touch Threshold Study of the touch threshold was carried out in the same fashion as that for pain. Table 268 provides a summary of the initial analysis done without reference to any control variables. For none of the nerves except the ulnar is there any evidence of association, but for the ulnar the evidence seems 54*

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fair (P<C.05). When the eight control variables were introduced into the analysis again only the ulnar seemed to display the association, which recurred with each subdivision of the material. Few of the control vari- ables appeared to offer any prospect of improvement in the association, however, and table 269 is confined to these. Further details of the associa- tion are shown in table 270 for two controls which do as much as any for the association between forecast and touch recovery. Again, as in the case of pain sensitivity, however, any association is too weak to have clinical value. 3. Skin Resistance (SR) Follow-up examiners classified their SR results according to the follow- ing scheme: Elevated in autonomous area. Elevated in total area. Decreased. Normal. Mixed patterns. The autonomous zones for autonomic fibers are less certainly known than the sensory, and there was some doubt as to the best handling of the SR data for the purposes of the present chapter, especially since cases with elevated SR in the autonomous zone had generally been given a lower forecast than cases with elevated SR in the total area of autonomic inner- vation. However, the decision was made to dichotomize the observations, regardless of the autonomous zone, into elevated SR versus other SR, with the omission of cases with "mixed patterns." As may be seen from table 271, which gives the mean values of the forecasts corresponding to this dichotomy any evidence of association between the summary forecast and SR is con- fined to the ulnar and peroneal (including sciatic-peroneal) nerves. When the control variables were introduced into the analysis little or no improvement resulted. Table 272 gives the results obtained when the selection of cases was confined to those with a single operation, for this factor seemed to do as much as any control variable for the association between the forecast and SR. In the ulnar and the peroneal the discrep- ancies remain greatest, but still not large in the light of the practical require- ments for useful forecasting. Table 273 shows the relationship in somewhat more detail for these two nerves; although the absence of cases with normal SR among those with low percentage forecasts is provocative, the amount of information is so small that no statistical significance can be attributed to the discrepancy. However, the gross comparisons exhibited in table 272, taken in the aggregate, do support the view that autonomic recovery bears some relation to the neuropathologist's forecast. As was observed for pain and touch, any association is weak. 352

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Table 273.—Summary Forecast of Regeneration and Skin Resistance, Ulnar and Peroneal Nerves Operated on Only Once Ulnar P eroneal ' Forecast (percent) Elevated skin resistance Normal, decreased skin resistance Elevated skin resistance Normal, decreased skin resistance Total Total 0-12 ... 1 o 1 3 o 3 13-22 2 o 2 2 o 2 23-32 2 0 2 1 3 4 33-42 1 0 1 0 0 0 43-52 4 3 7 6 3 9 53-62 3 2 5 2 1 3 63-72 8 5 13 3 2 5 73-82 .... 0 2 2 0 1 1 93- 0 0 0 0 0 0 Total 21 12 33 17 10 27 1 Including sciatic component. 4. Motor Recovery It will be recalled from chapter III that motor recovery may be ap- proached via several indices, the most summary being the modified British classification which is subject to some center variation. Although the most reliable motor observation is the measured strength of individual muscles, the more summary indices were explored first, and only after it became apparent that any relationship between the forecast and motor recovery was probably weak were tabulations extended to a few representative muscles as a final check. Table 274 provides a summary of the relationship between the neuropathologist's forecasts and the British classification. At best the evidence there seems suggestive in the statistical sense; only for the peroneal is the discrepancy of any real magnitude. The tabulations were then extended by introducing the eight control variables. Most of these resulted in some strengthening of the evidence of association between fore- cast and motor recovery in the upper extremity, but were without effect in the lower extremity. The evidence of association seen in table 274 for the peroneal is reflected in each of the 8 separate tables and to about the same extent, whereas none of the control variables provides more evidence of association in the tibial than table 274 shows for this nerve. The control variables which seem best able to support the association between forecast and motor recovery are site (for ulnar lesions) and number of operations (for median lesions), and table 275 presents the tabulated detail. Parallel data for peroneal lesions are given in table 276 for all lesions studied, since 559

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none of the control variables improved the evidence of association between forecast and recovery. Taken all together the evidence points to a definite but somewhat weak association between the neuropathologist's forecast and motor recovery. Motor recovery in the lower extremity was also explored on the basis of number of affected muscles able to contract voluntarily at the time of follow- up, with substantially the same results as were obtained with the British summary of motor recovery. The muscles studied in this way, and their classification as proximal or distal, are discussed on pages 106-113. Table 277 provides the mean values of the neuropathologist's forecasts for cases classified as to number of affected muscles able to contract voluntarily at follow-up. Again the evidence of association is at least suggestive for peroneal injuries, but within the range of chance variation for the tibial. Table 275.—Summary Forecast of Regeneration and British Classification1 of Motor Recovery, for Median and Ulnar Lesions With Specified Controls Median, operated upon only once Ulnar at or below elbow Forecast of regeneration A' B' A" BI 0-12 0 1 0 0 0 0 1 0 2 5 3 1 1 0 3 0 3 4 4 0 0 0 0 3 0 2 3 6 0 0 13-22 23-32 33-42 1 43-52 2 53-62 2 4 0 0 63-72 73-82 83-92 Total 10 12 15 14 Moan rating 51.6 66.2 48.5 54.5 1 In every case calculated here proximal muscles were acting against gravity, so that two classes were denned on the basis of the modified British scale: A—Proximal muscles acting against gravity or against resistance, intrinsic muscles showing at most perceptible contractions. B—Both proximal and distal muscles contracting against resistance. These correspond to the following rubrics given in detail on page 115. A—Groups 2 and 3. B—Groups 4, 5, and 6. 408980—07 18 561

Table 276.—Summary Forecast of Regeneration and British Classification of Motor Recovery, for All Peroneal and Sciatic-Peroneal Sutures British summary of motor regeneration ' Forecast of regeneration Perceptible contraction in proximal muscles, none in intrinsics No con- traction A B Total 0-12 . . 1 2 4 1 4 0 1 0 0 2 0 2 2 7 2 0 0 0 0 1 2 0 0 0 0 0 1 1 0 0 3 3 8 3 15 4 5 1 0 13-22 23-32 33-42 0 4 1 3 1 0 43-52 53-62 . ... 63-72 73-82 83-92 Total 13 15 12 2 42 Mean rating 34.2 39.3 49.6 62.5 41.8 1 Rubrics A and B have the meanings specified in table 275. Table 277.—Mean Summary Forecast of Regeneration and Number of Affected Muscles ' Contracting Voluntarily at Follow-up, Peroneal and Tibial Injuries Peroneal and sciatic - peroneal Tibial and sciatic- tibial Number of muscles contracting Number of nerves Mean fore- cast (per- cent) Number of nerves Mean fore- cast (per- cent) A. Four proximal muscles affected 0-3 27 13 34.7 52.6 14 8 41.5 45. 1 4. . . Total 40 40.5 22 42.8 0 B. One distal muscle affected 22 10 46.9 1 38.5 Total 32 44.3 1 In standard list of muscles (p. 73). 562

In planning the statistical correlations of pathological assessments and motor recovery it was thought unnecessary to provide for analyses based on individual muscles, and the design of the punchcards proceeded accord- ingly. However, one of the motor fields contains the average power of distal muscles in the standard set, and two nerves are represented by single muscles, the median by the abductor pollicis brevis and the tibial by the interossei. In view of this specificity it was decided to study the average power of distal muscles 2* in relation to the summary pathological rating. In the lower extremity there is too little variation in the power of movement against resistance for this approach to have any value, but for the upper extremity the results of the correlation study are as follows: No. of Correlation coefficient l Nerve lesions P \fr-Hian 24 +.27 >.05 Radial 16 + . 12 >.05 Ulnar 48 + .22 >.05 All three combined 88 + .22 .05 1 Product-moment coefficient. All three independent coefficients are small and positive, with none outside the chance range; in the aggregate they have a probability of .05 under the hypothesis of independence. There is, then, only borderline evidence of association between the summary forecast and actual power at follow-up. 5. Overall Functional Evaluation As described in the following chapter, functional performance was evaluated with the aid of an 11-point scale (0, 10, . . . 100 percent) de- veloped by Dr. Lewey, and as the most summary evaluation of recovery it seemed attractive to compare the neuropathologist's forecasts with these functional ratings. The material was tabulated separately for the upper and lower extremities and table 278 gives the mean summary forecast for each point on the scale of useful function. For neither upper nor lower extremity lesions is there statistical evidence of association. 6. Composite Index of Nerve Regeneration Except for Dr. Lewey's functional rating, the foregoing analysis deals with single modalities of recovery, and it was thought desirable to test the pathologist's summary rating against a composite index of regeneration less dependent upon the performance of useful functions. Pain, touch, SR, and motor recovery were chosen as the bases for this index, and a ** The distal muscles are specified on p. 73. 563

simple dichotomy defined for each nerve and for each modality so that all nerves might be combined. Pain: Median and peroneal: threshold of 30 gm. or more v. <30 gm. Ulnar and tibial: threshold of 40 gm. or more v. <40 gm. Radial: threshold of 20 gm. or more v. <!20 gm. Sciatic components: at most deep pressure v. threshold of 40 gm. or less. Touch: Median, ulnar, radial: threshold of 16 gm. or more v. <16 gm. Peroneal and tibial: threshold of 25 gm. or more v. <25 gm. Sciatic components: threshold )>50 gm. v. 50 gm. or less. SR; All nerves: elevated in autonomous or total area v. normal or decreased SR. British Motor: All nerves except sciatic-tibial: no more than perceptible contraction in intrinsici v. intrinsics moving against resistance. Sciatic-tibial: no return in intrinsics v. any return in intrinsics. Table 278.—Mean Summary Forecast of Regeneration and Overall Functional Evaluation at Follow-up Upper extremity Lower extremity Scale of function Number of cases Mean forecast Number of cases Mean forecast 0 1 2 3 5 2 14 18 22 23 9 1 5 3 0 0 0 4 7 15 25 21 2 0 28 10 50 37 54 45 59 55 55 48 67 40 20 30. .. 40 34 26 50 60 46 48 42 70 80 90 58 100 Total 100 54 77 42 If each such dichotomy is represented as 0 or 1, depending on whether recovery is poorer (0) or better (1), then the lesions on each nerve or group of nerves will fall into 16 subgroups ranging from 0000 (poorer in all 4 modalities) to 1111 (better in all 4). The dichotomies were designed to facilitate the combination of the several nerves, and for purposes of analysis the 16 subgroups were combined on the basis of the number of 1 's, ranging from none to 4. From the tabulated result which appears in table 279 the only possible conclusion is that the predictive value of the summary forecast is not improved by combining the four modalities in this fashion; the vari- ation among the means presented there is well within the range of chance.

E. SUMMARY Over 600 cases of peripheral nerve suture were studied during World War II by an histologist working with a group of neurosurgeons with a view to evaluating the microscopic quality of sutured ends. The records of the findings have been deposited in the form of reports, photomicrographs, microscopic sections, etc., in the Armed Forces Institute of Pathology. An effort has been made to forecast peripheral nerve regeneration on the basis of this material, and these predictions have been correlated with the results of follow-up examinations made in the five clinical centers as part of the larger follow-up study. The mechanics of correlation have been in the hands of the statistician for the follow-up study. Table 279.—Mean Summary Forecast of Regeneration and Composite Index of Regeneration Number of modalities with regeneration rated favorably Number of lesions Mean rating 0 18 48.33 1 33 51.67 2 37 49.59 3 31 52.90 4 6 53.33 Total 125 50.96 Follow-up status was represented by the pain and touch thresholds, skin resistance, several indices of motor recovery, and overall functional recovery. Not all functions subserved by the periphal nerves were represented, and those that were represented often were only partially covered, as in the restriction of observations on pain and touch to the autonomous zones. Nevertheless, if the follow-up observations be regarded as a sam- pling on the basis of which recovery might be roughly scaled, the represen- tion of modalities would appear to be adequate for the present purpose. The neuropathologic assessments were made in terms of changes in four regions of the nerve, seen in cross section: epineural, interfascicular, peri- neural, and intrafascicular. The neuropathologist evaluated the fibrous or neuromatous changes evident in each individual region and assigned to that region a numerical value representing the relative loss in recovery he ex- pected from these defects. He did not make separate forecasts for fine fibers carrying pain and autonomic impulses and for the larger fibers carrying pressure, touch, and motor impulses. For each segment (distal or proximal) the estimates for all four regions were summed to represent the anticipated influence of all the defects present in that segment. The overall rating was then obtained on the assumption that the defects in the two segments were independent; specifically, the complements of the estimated

percentage losses for the two ends were multiplied to provide a numerical estimate of recovery for the nerve as a whole. It was, of course, regenera- tion across the gap at which the predictions were aimed; other character- istics of the lesion and associated injuries were known and could be inte- grated with the neuropathologic assessments as required. Any such index is undoubtedly an arbitrary one, and it may seem presumptuous to apply a percentage scale to the pathologic phenomenon of fibrosis in different cross- sectional areas of nerves. However, the most that was hoped for was that in its clinical application the overall summary might permit a rough segre- gation of cases into those with good, bad, and indifferent nerve ends. Analysis of the neuropathologist's ratings on the 181 nerve lesions studied here shows that the intrafascicular region of the distal segment is the chief source of variation in the final estimates. The severest penalties were always applied to the nerves with more advanced degrees of distal tubular shrinkage, and it was rare that defects in other regions were considered prejudicial to any appreciable extent. The ratings vary somewhat by nerve, chiefly in that those of the upper extremity were given a better chance of recovery than those of the lower. The ratings were not found to vary by site of lesion, but both the length of gap and time interval from injury to suture were seen to be inversely correlated with the neuropathologist's overall estimates of regeneration. The correlations have been sought for each modality or other index of recovery, separately by nerve and for all nerves combined, but without developing more than suggestive evidence of association. Various charac- teristics of the lesion and its handling, e. g., time and length of gap, have also been introduced as control variables, but without adding appreciably to the evidence of association. Summary tables are included as a record of these analyses, together with a master table showing the necessary data for each lesion. On balance the view is taken that a definite association probably does exist, especially for SR and voluntary motor function, but that the relationship is too weak for clinical usefulness. As already noted, the severest penalties were always applied to the nerves showing the most advanced degrees of distal tubular shrinkage, a phenome- non shown to be pronounced 5 months or longer after nerve severance. There were 30 cases with poor assessment ratings, and in the correlation tables they were equally distributed among good, bad, and indifferent classes of muscle recovery. Since voluntary motor fibers are usually con- sidered to be large in caliber and well myelinated, the good and fair results under adverse histologic circumstances suggest that shrunken neurilemmal tubules may be redistended, or that voluntary contraction of muscle may be accomplished even though the effector fibers may not regain their normal girth or state of myelination. Case reports, including illustrations, have been presented for a represent- ative group of cases. The photomicrographs of the nerve ends have provided what may be regarded as the most plausible explanation of the poor functional results in cases considered to have had little or no pathologic

alterations in the nerve ends at the time of suture. The mismatching of proximal and distal fascicles, an invariable result of the resection and suture of nerve stumps, has been demonstrated, and is considered to be a most important factor in producing imperfect redistribution of nerve fibers and, therefore, subnormal functional recovery. On the rare chance that the above findings be wrongly interpreted as evidence against careful resection to good tubules preparatory to anasto- mosis, it must be pointed out that the range of variation in the quality of nerve ends studied here is actually a small one. Had surgeons not uni- formly cut back the injured segments to achieve the best ends they could provide within the limitations imposed by the gaps to be bridged, the results reported here, and in the motor chapter where a small effect seemed associated with the quality of the nerve ends, would probably have been very different. On an absolute scale, nerve ends range in quality from those produced by the surgeon's scalpel to the blunt, neuromatous bulbs commonly presented to the surgeon exploring war injuries. Only the better part of this absolute range is adequately represented in the material studied here, and the findings, therefore, pertain only to that part of the range. They must not be taken as any discouragement to painstaking resection preparatory to anastomosis. 567

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In peacetime, the busiest civilian clinics do not see enough peripheral nerve injuries to permit authoritative conclusions to be drawn about their management. In World War I, large numbers of these injuries were skillfully cared for by a small group of pioneer neurosurgeons, but there was no comprehensive follow-up and the opportunity to use the experience to the fullest possible extent was lost.

The publication of Peripheral Nerve Regeneration: a Follow-Up Study marks the end of a huge clinical research program that began in 1943, in the course of World War II. The program was participated in by more than a hundred of the neurosurgeons who served in the Medical Corps, as well as by many neurologists, neuroanatomists, neurophysiologists, neuropathologists, physical therapists, statisticians, and representatives of the administrative personnel of every echelon of command in the Army Medical Corps. Later the program was also participated in by representatives of the Veterans Administration and the National Research Council.

The primary purpose of this study was to evaluate the suites of peripheral nerve injuries sustained in World War II, with the hope of standardizing such treatment for future wars and, where possible, for similar injuries of civilian life. The secondary purpose of this study was to discover nerve injuries among veterans of all services that still required remedial measures. Peripheral Nerve Regeneration: a Follow-Up Study describes the final level of regeneration in representative cases of complete suture, neurolysis, and nerve graft, examines the apparent influence of gross characteristics or the legion, and or associated injuries, upon final result, and evaluates predictions of final recovery based on gross and histologic study of tissue removed at operation. The report of this study of postwar nerve regeneration provides for the surgeons of the future a body of information upon which they may guide repair of injured peripheral nerves and initiate needed orthopedic rehabilitation.

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