Reprinted from THE JOURNAL OF HAND SURGERY, St. LouisVol. 13A, No. 3, pp. 345-351, .May, 1988, (Printed i~n the U.S.A.)(Copyright © 1988, by The C.V. Mosby Company)

Evaluation of mic:rosurgical internal neurolysisin a primate media~t nerve model of chronicnerve compression

This Study evaluates theeffect of internal neurolysis on a cin’onically compressed primate me~iian

nerve as tompared with a simple-decompret~sion procedure. In 11 adult, cynomologous monkeys,the median nerve in the carpal tunnel was banded with a silicone tube. After 6 months of nervecompreSsion (mild to moderate compression in our model) in eight monkeys, a microneurosurgicalint-ernal neurolysis was carried outon the median nerve of one hand and a simple decompression-(removal of band) was carried out on the median nerve of the other hand. Histologic, morphologic,and electrophysiologic evaluation .was carried out 6 months later. Six control animals were

similarly evaluated after 0, 6, and 12 months of nerve compression. The degree of compressionproduced was not severe in that it did not cause Wallerian degeneration. Histologic and elec-trophysioiogic improvement was produced in both treatment groups over the two chronicallycompressed groups (6 and 12 months of compression). While internal neurolysis did not causeintraneural scarring or nerve fiber dmnage as compared with simple decompression alone, therewas no difference noted between the effecl~ of these two treatment methods on the chronicallycompressed nerve. (J HANDSURG 1988;13A:357-63.)

Susan E. Mackinnon, MD, FRCS(C), FACS and

A. Lee Dellon, MD, FACS, Toronto, Ont., Canada and Baltimore, Md.

While peripheral nerve entrapment is a

common problem treated by the hand surgeon,~’3 thepathophysiology associated with this entity is not co~a-pletely understood and controversy exists regarding ap-propriate surgical treatmen~ measures. It has been sug-

gested in both experimental studies and clinical reports--~-at-i-n-te-~ al--n-e tit o ly-s i-s ~:aa~ es-i~tra~e a rzd-ffib-r t rsts-:and

nerve fiber damage as compared with simp!e de-

From the Division of Plastic Surgery and Neurosurgery, Johaas Hop-kins University, Baltimore, and the Division of Plastic .Surgery,Department of Surge~, University of Toronto, Ont., Canada.

Received for publication¯ March 3, 1986; accepted in revised formJune 2, 1987.

Funded l~y the Physicians Services Incorporated Research FoundationServices with Support from the Plastic Surgery Education Foun-dation, Sunnybrook Medical Research Foundation and the Ray-mond M. Curtis Research Foundation.

Presented at the American Society for Surgery of the Hand,New Orleans, February, 1986.

No b~nefits in any form have been received or will be received froma commercial party related directly or indirectly to the Subject ofthis article.

Reprint.requests: A. Lee Dellon, MD, 3901 Greenspring Ave., Suite104, Baltimore, MD 21211.

Fig. 1. The experimental design involved compression of themedian nerve for 6 months followed by either decompressionor internal neurolysis.

compression alone. In spite of this controversy, therehave been only two experimental studies addressing thisproblem?’ 5 This study was designed to evaluate the

effect of internal neurolysis of a chronically compressed

THEJOURN.ALOFHANDSURGERY345

346 Mackinnon and Dellon

The Journal ofHAND SURGERY

.... Fig. 2. After 6 months of chronic compression, the median nerve wasneurolysed. Inset: An internalneurolysis into four fascicular groups was carded Out in this median nerve.

Table I. Morphologic assessment

Compression(mo) Treatment N

¯~Fiber diameter I Perineurium

(tz) ( +-SEM)I

(1~) ( +-SEM)

0 3 6.6 --- 1.3" 6.0 - 2.4*6 3 4.6 +-- 1.6 15.0 - 2.5

12 3 4.3 --- 0.6 16.8 - 5.56 Neu(otysis 8 5.2 ---’0.5 13.4 +- 2.66 Decompression 8 4.9 -+ 0.8 13.5 ± 2.8

*p < 0.05.

median nerve in a primate model as compared wil~a nerve with 3.5 loupe magnification (Figs. 1 and 2).

.............. ff~fm~-~m~le d~c~p~pres-~i~nz-. ................ ± ..... .... The~neuroiysis-was-begun-proximal-to-the-region-ofcompression at the level of the epineurium, and an

Mater~al and methods

Using a model for chronic ̄ nerve compression in tilepalmate6 in 11 adult cynomolgus monkeys, with themonkeys under ketamine and acepromazine anesthesia,the median nerve in the carpal tunnel was exposed andbanded with a 1 cm length of silicone tubing (internaldiameter of 1.98 mm). The silicone tubing was closed

¯3vith three interrupted No,. 8-0 nylon sutures so that tl~etubing fit snugly about the nerve~ The transverse carpalligament and skin were closed with No. 3-0 nylon su-ture. One million two hundred thousand units of pro-caine pencillin was administered intramuscularly duringthe operation. Similar procedures were carded out inboth hands. No splints were used postoperatively. Afl:er6 months of nerve compression in eight animals, aninternal neurolysis was carded out on the right median

extensive internal neurolysis was carried out with re-moval of the epineurium and dissection of the mediannerve into four to six fascicular groups (Fig. 2). Carewas taken not to damage the perineurium. At no timewere any windows in the perineurium noted to indicateperineurial damage.7 In these same eight animals, sim-ple decompression (release of the transverse carpal lig-ament and removal of the silicone band) was carriedout in the left hand. In.three other adult control animals,~amples for biopsy from the right median nerve weretaken at 6 months for histologic evaluation. Six monthslater, the median nerves were harvested from the eightexperimental animals and light and. electron micro-sfopic evaluation was carded out studying the nerveproximal and distal to the carpal tunnel, as well asthrough the carpal tunnel region. Samples for biopsy

Vol. 13A, No. 3May 1988 Evaluation of internal neurolysis 347

Fig. 3. A, The normal architecture of the cynomologous median nerve is demonstrated withthe perineurium (arrow) noted and a population of well myelinated fibers. B, After 12 monthsof nerve compression, thickening of the perineurium and internal epineurium with thinning ofthe myelin is noted. C, Six months after decompression of the chronically compressednerve, improved architecture of the median nerve is noted, with thinning of the perineurium andthinning of the internal epineurium. D, Six months after internal neurolysis, there was nohistologic difference between this nerve and the nerve that was decompressed. SubperineurialRenaut bodies are noted (arrow). Transverse section. (Toluidine blue stain. Original magnifi-cation, × 92.)

were taken from the three animals in which the siliconebands were left on the left median nerve for the full 12month course of the sttidy. In this study, 12 months ofcompression would represent the natural progression ofuntreated compression neuropathy.

I-Iistologic evaluation. The median nerves were har-vested en bloc beginning proximal to the carpal turmeland extending distally to the region of nerve compl:es-sion. These nerves were fixed with Karnowskyls fix-ative and post fixed with osmium tetroxide and embed-ded in Araldite 502 (Ciba-Geigy, Canada). Sections ixm were stained with toluidine blue and examined" bylight microscopy.

Electron microscopic sections were examined on a

Philips 300 61ectron microscope (Philips Electronic In-struments, Mt. Vernon, N.Y.) after lead citrate stained

sections were cut with a LKB II ultramicrotome (LKB,Productur, AB Bromma, Sweden).

Morphologic evaluation was carried out by means ofdigitizing pad (Bioquant II, R & M Biometrics, Nash-ville, Tenn.), with computerized (IBM) linked digitalpen at x 800 magnification. Fiber ,histograms wereobtained and with the use of standard grid areas(37,500 ~m:) axon and fiber areas were determinedand axon and myelin and axon and fiber ratios werecalculated.

Electrophysiologic studies. By Teca instrumenta-tion (TECA TE 42), electrophysiologic recordings werecarried out at 0, 6, and 12 months and after 6 monthsof either decompression or internal neurolysis. Motor¯ amplitude and latencies were determined stimulatingthe nerve proximal to the wrist and recording from the

348 Mackinnon and Dellon

The Journal ofHAND SURGERY

MORPHOMETRIC ASSESSMENT

Axon/Myelin

o

12 6+ 6+Decompression Neurol

Fiber.Diameter

7

3

2

1

20

15

Perineurial ,Thickness lO

5

* p<0.0s

Compression (months)

Fig. 4, The data lisied in Tables I and II is graphically outlined. No parameters measured returnedcompletely to normal after either treatment method. There was no statistical difference noted between.the two treatment groups.

thenar muscles. Orthrodromic sensory recordings wereobtained by stimulating the index finger and recordingproximally on the median nerve.

Results

After 6 and 12 months of banding of the mediannerves, changes were noted in both the nerve fibersand the connective tissue layers of the nerve that wereindicative of changes of chronic nerve compression8’ 12

(Fig. 3). Morphometric findings are detailed in Ta-bles I and H and graphically in Fig. 4. Thinning of themyelin was noted with subsequent decrease in the per-centage of myelin and increase in the axon and myelinand axon and fiber ratios. ThicKening of the interfas-cicular epineurium and perineurium was also noted(Tables I and II, Fig. 4). After 6 months of compression,there was evidence of only mild to moderate compres-sion. After 12 months, severe compression with Wal-

Vol. 13A, No. 3May 1988 Evaluation of internal neurolysis 3~19

Fig. 5. A, In the normal cynomologous median nerve, a population of well my~linated fibers isseen. B, After 6 months of chronic nerve compressiori, there is thinning of the myelin. C, After12 months of chronic nerve compression, progressive thinning of the myelin is noted with anapparent increase in the population of the thinly myelinated small fibers. D, After simpl~ de-compression or internal neurolysis, the fiber population demonstrated some thickening of the myelinalthough the fibers did not return to normal (Fig. 4, A). This micrograph is taken from a neurolysednerve. Transverse section. (Toluidine blue stain. Or!ginal magnification, × 588.)

Table II. Axon :myelin ratio

x Area ± SEM (tz2)

Axon ̄ Myelin - FiberCompression

(mo)

06

126+

Neurolysis6+

Decompression

34.6 ± 1.14 57.6 +-- 2.3* 92.2 --- 1.13’31.4 ÷- .87 27.5 --- 1.10 58.9 --- 1.4134.8 ± 1.30 17.9 ± 1.19 52.1 ± 1.55

27.0 --- 0.01 26.2 - 0.10 53.3 --- 0.14

28.4 ÷ 0.01 24.8 --- 0.08 53.2 ± 0.19

% Myelin . Axon/myelin

6346.34

Axon/ fiberG-ratio)

0.60 O.381..14 0.531.90 0.67

50 1.04 0.50

46 1.17 0.53

*p < 0.05.

lerian degeneration was noted. After internal nettrol-

ysis or simple decompression, histologic evalu~.tion(Figs. 3 and 5) and morphologic assessment (Tab]les and II) demonstrated an improvement in all factors raea-

sured when comparison was made with those nervesthat had been compressed for 6 and 12 months. Therewas no statistical difference (paired Students t-test) be-tween either treatment group. None of the parameters

350 Mackinnon and DellonThe Journal of

HAND SURGERY

NERVE" CONDUCTION STUDIES4

3MotorLatency(m / sec) 1 .

(K)4~0~)I "~ ";"’~~""~ :Y!~

Latency

/ ¯0 6 12 6+ 6+

¯p <.05 Compression (months) Decompression Neurolysls

~ig. 6. The elcc~ophysMog~c~oups w~s ~otcd.

measured in either treatment group returned to normalvalues.

Progressive deterioration of electrophysiologic statuswas noted in both sensory and motor latency and am-plitude after 6 and 12 months of nerve compression.While there was some improvement in these parametersafter n_eurolysis or simple decompression, there was nostatistical difference noted between these two treatmentgroups (Fig. 6).

¯ Compression of the median nerve of the cynomolgusmonkey, which contains 16 - 5 fascicles, 6 producesprogressive nerve fiber and connective tissue changesat 6 and 12 months. Histologic, morphologic, and elec-trophysiologic assessment of the two treatment groupsdemonstrated no difference between these groups butimprovement was noted in all parameters when the twotreatment groups were compared with the nontreatmentgroup at 6 and 12 months.

In this study, the neurolysis performed was extensiveDiscussion ¯ ¯ " ¯................................................. . .................................. (eomptete-mterfaseaeutar ~ptneureetomy)-ln--order

The role of internal neurolysis in the management of stress the hypothesis that neurolysis would not causethe patient with nerve injury is as controversial today¯ as it was when first described in the early 1900S.13":t7

Several authors support the use of intemal neurolysisin the management of carpal, tunnel syndrome,18"::~

Phalen,23 however, has cautioned that "inevitable in-terfascicuIar scarfing cat~. produce irreparable damageto the median nerve" after internal neurolysis. Lund-borg, Rydevik, and Nordborg~ noted that "internal neu-rolysis per se implies a significant trauma to the nerveand may induce microvascular damage and formationof new intraneural scar tissue." Hudson et al? con-cluded that a carefully performed internal neurolys:iswould not PrOduce "any significant long lasting mo:r-phological or physiological alterations in a peripheralnerve." Both studies were done on normal, subprimal:enerves made up of only a few fascicles.

fiber pathology or scarring. In the clinical situation, theappropriate internal neurolysis is a "stepwise’’~ neu-rolysis preceding from epifascicular epineurotomy toepifascicular neurectomy to partial to complete inter-fascicular epineurectomy. Thus, frequently the neuro-lysis required clinically will be far less than that carriedout in this study.

.In this study, internal neurolysis did not confer im-proved histologic or electrophysiologic results as com-pared with simple decompression alone. It is empha-sized that neurolysis was carried out after only 6 monthsof nerve compression. At this time, there was no evi-dence of Wallerian degeneration (the clinical counter-part being muscle atrophy and abnormal two-point dis-crimination). Our understanding of the histopathologicpicture of chronic nerve compression .is a spectrum

Vol. 13A, No. 3May 1988 ’ Evaluation of internal neurolysis 351

: .... .... ~ endoneurial microvessels. By contrast, the nerve fibers

i ........~ ..... ~ ~-:.-.-. " ¯ . themselves varied from normal to degenerated in dif-

......... . ..~ ¯ .......... ferent patients.Since the clinical correlates of morphometric abnor-

malities are not known, the experimental design of this

study will not permit this data to be interpreted in te~msof which treatment group gives better hand function or.improved symptoms. While a direct comparison cannotbe made between histology, electr0physiology, andnerve function, the results of this study would confirmclinical experience that dictates that in mild to moderatenerve compression, simple decompression alone willyield excellent clinical results.

We would like to thank Dr. Raymond M. Curtis for hisunlimited enthusiasm and support given in 1981-82 when thepreliminary studies ’leading up to this report were initiated.The authors are indebted to Dr. A. R. Hudson, Professor andChairman, Division Neurosurgery, University of Toronto, andDr. W. W. Eversman, Jr., for their critical evaluation of themanuscript and to Mr. Daniel Hunter, electromicroscopist,for his comprehensive tissue evaluation. The authors thankMr. W. A. Seiler IV, chief microsurgical technician, for hissuperb help throughout the course of the study, and Mr. R.Schlegel, chief of physical rehabilitation at Union MemorialHospital, for his technical expertise in carrying out the nerveconduction studies.

extending from changes in the blood nerve barrier and

regional ischemia to Wallerian degeneration. A histo-logic study of human chronic nerve compression dem-onstrated that patients complaining of identical symp-toms demonstrated very different histologic changes intheir nerves.25 In four human nerves studied, all spec-

. imens demonstrated changes in the perineurium and-

7. Spencer PS, Weinberg H, Raine CS, Prineas JW. Theperineurial window A new model of focal demyelin-ation and remyelination. Brain Res 1975;96:323-9.

8. Mackirmon SE, Dellon AL, Hudson AR, Hunter DA.Chronic nerve compression: An experimental study inthe rat. Ann Plast Surg 1984;I 3:I12~20.

9. Neary D, Ochoa J, Gilliatt RW. Subclinical entrapmentneuropathy in man. J Neurol Sci 1975;24:283-98:.Neary D, Eames RA.-The..pathology of ulnar nervecompression in man. Neur0p~tl~61 Appl Neurobiol 1975;1:69-88. - -Thomas PK, Fullterton PM. Nerve fiber size in the carpaltunnel syndrome. J Neurol Neurosurg Psychiatry 1963;26:520-7.Mackinnon SE, Dellon AL, Hudson AR, Hunter DA.Histopathology of chronic compression of the superficialradial nerve in the forearm. J HAND SURG 1986;11A:

¯ 206-10Babcock WW. Nerve disassociation: A new method forsurgical release of certain painful or paralytic afflictionsof nerve trunks. Ann Surg 1907;46:686-93.Babcock WW. A standard technique for operations onperipheral nerves with a special reference to the closureof large gaps: Surg Gynecol Obstet 1927;45:364-78.Lehmann W. Allgemeine therapie. Foester O, et al, eds.Berlin: Springer Verlag, 1936:165-205.Stopford JB. Compression of peripheral nerves. BrMed J 1926;1:1027-8.

17. Murphy JB. Cicatrical fixation of ulnar nerve fl:om an-cient cubitus valgus release and transference to newsite. Clin John B. Murphy 1916;661-79.

18. Curtis RM, Eversmann WW, Jr. Internal neurolysis asan adjunct to the treatment of the carpal tunnel syndrome.J Bone Joint Surg [Am] 1973;55:733-40.

19. Rhodes CE, Mowery CA, Gelberman RH. Results of- internal neurolysis of the median nerve for severe carpaltunnel syndrome. J Bone Joint Surg [Am] 1985;67:253-6. ........................................

20. Samii M. Intraneurale neurolyse des ner.vus medianusbeim karpal tunnel syndrom. Hand Chirurgie 1976;8:117-9.

21. Levine J, Spinner M. Neurolysis on elderly patients. ClinOrthop 1971;80:13-16.

22. Brown BA. Internal neurolysis in traumatic peripheralnerve lesions in continuity. Surg Clin North Am !972;52:1167-75.

23. Phalen GS. The birth of a syndrome, or carpal ~unnelrevisited. J HAND Sug6 1981;6:t09-10.

24. Millesi H. Internal neurolysis. In: Gorio A, Millesi H,Mifigrino S, eds. Posttraumatic peripheral nerve regen-eration: Experimental basis and clinical implications.New York: Raven Press, 1981:197-208.

25. Mackinnnn SE, Dellon AL, Hudson All, Hunter DA.Chronic human nerve compression. Neuropattml ApplNeurobiol. (In press.)

10.

11.

.12.

13.

14.

15.

16.

REFERENCES

1. Eversman WW Jr. Compression and entrapment neurop-athies of the upper extremity. J HAND SURG 1983;8:759.

2. Spinner M. Injuries to the major branches of peripheralnerves of the forearm. 2nd ed. Philadelphia: WB Saun-ders, 1978.

3. Dawson DM, Hallet M, Millender LH. Entrapment neu-ropathies. Boston: Little, Brown & Co, 1983.

4..Rydevik B, Lundborg C, Nordborg D. Intraneural tissuereactions induced by internal neurolysis. Scand J ]?lastReconstr Surg 1976;10:3-8.

5. Gentili F, Hudson AR, Kline DG, Hunter DA. Idor-. phological and physiological alterations following inter-.nal neurolysis of normal rat sciatic nerve. In: Godo A,Millesi H, Mingrino S, eds. Posttraumatic peripheralnerve regeneration: Experimental basis and clinical! im-plications. New York: Raven Press,. 1981:183-96.

6. Mackinnon SE, Dellon AL, Hudson AR, Hunter DA. Aprimate model for chronic nerve compression. J ReconstrMicrosurg 1985;1:185-94.