Idiopathic carpal tunnel syndrome: Histologic study of flexor tendon synovium The histologic lesions in flexor tendon synovium of 21 patients seen initially with idiopathic carpal tunnel syndrome have been studied. The findings were similar in all biopsy specimens and were typical of a connective (J HAND
tissue undergoing
degeneration
under repeated
mechanical
stresses.
SURG199O@A:497-503.)
F. Schuind,
MD, M. Ventura, MD, and J. L. Pasteels, MD, PhD, Brussels, Belgium
T
here are numerous clinical settings in which carpal tunnel syndrome occurs. l-7 However, in many patients, no specific cause can be found. The idiopathic form of carpal tunnel syndrome (CTS) occurs more frequently in women, with a peak age range from 40 to 60 years; it is commonly bilateral.8~‘0 Although the disease is very common, its pathophysiology is still not clearly understood. It has been assumed that, in these cases, the median nerve compression is related to a nonspecific synovitis around the flexor tendons. ‘. ‘, *,9, 1o-19This study describes the histologic lesions found in the flexor tendon synovium.
Methods Between February 1985 and August 1987,38 patients had operations to treat 44 carpal tunnel syndromes at the Cliniques Universitaires de Bruxelles, Hopital &asme, by F. S. To study a selected series of “pure” idiopathic CTS , only 2 1 patients fulfilling the following criteria were included in the study: (1) Typical signs and symptoms of carpal tunnel syndrome14; (2) No significant past medical history, i.e., no history of trauma, of hand or wrist infection, of wrist fracture or of other bone or joint wrist injury, no diabetes mellitus, gout, amyloidosis, or any other metabolic or endocrine im-
balances, no history of rheumatoid arthritis or other related disease’; (3) abnormalities in the preoperative electrodiagnostic studies, i.e., prolongation of the distal motor latency beyond 4 msec, or prolongation of the distal sensory latency beyond 3.5 msec14. ‘a. 21; (4) normal standard hand and wrist and carpal tunnel roentgenograms; (5) normal basic laboratory work (sedimentation rate, blood sugar levels, serum uric acid, T3 and T4 levels); negative latex test; (6) at operation, no evident cause of compression of the median nerve in the carpal tunnel, other than thickening of the synovium around the flexor tendons (no vascular or muscular abnormality; no localized tumor); (7) significant postoperative clinical and electrodiagnostic recovery of the median nerveI 22; to be included in the study, the minimum follow-up duration was 6 months; the postoperative electrodiagnostic studies were done 3 months after the surgical procedure. The synovium tissue samples were fixed in Bouin’s solution. The histologic sections were stained by hematoxylin and eosin. All the histologic studies were done by J. L. P. The lesions were compared with samples of synotaken from patients without CTS vium tissue, (Fig. 1). Materials
From the Department of Orthopedics and Traumatology, Hopital Erasme, Cliniques Universitaires de Bruxelles, and the Laboratory of Histology, Brussels School of Medicine, Universite Libre de Bruxelles, Brussels, Belgium. Received for publication July 12, 1989.
Dec. 16, 1988; accepted
in revised form
No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. Reprint requests: F. Schuind, MD, Department of Orthopedics and Traumatology, Hopital Erasme, Cliniques Universitaires de Bruxelles, 808, route de Lemrik, 1070 Brussels, Belgium. 3/l/15628
Twenty-one patients were included in the study; 24 carpal tunnel releases.were done. The average age of the patients was 49 years (range, 32 to 81 years). There were 19 women and 2 men. Results In all biopsy specimens, the histologic findings were similar (Figs. 2 through 4). There was always a fibrous hyperplasia of the synovial membrane, with increased amounts of collagen fibers. The collagen itself was very irregular and disorganized. THEJOURNALOFHANDSURGERY
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Fig. 1. Normal flexor tendon synovium, taken from a patient without carpal tunnel syndr.ome (the carpal 1:unnel was opened during flexor tendon surgery). (Magnification X 1000.)
Table I. Histologic-clinical
correlation
Histologic grade
Mean age of the patients (yr) Mean preoperative delay of the symptoms (mo) Associated chronic “tendinitis” of the ipsilateral upper limb (%I) Mean distal motor latency (msec) Abductor pollicis brevis paralysis, thenar atrophy (%)
II
53 27 42 6.3 0
III
48 31 36 6.8 33
In more advanced lesions, localized areas with rarefaction, or sometimes with total disappearance of the fibroblasts, could be found (Fig. 2, A, Fig. 3, A, and B). In these necrotic areas, the collagen fibers showed fragmentation in eosinophilic debris, demonstrated by small (diameter, a couple of microns) rounded corpuscules (“rice” degeneration, Fig. 4), or even by a homogeneous necrotic “pap.” Beside these necrotic areas, the surviving cells were sometimes disposed like cords or in small accumulations of rounded cells, similar to chondrocytes (chondroid metaplasia, Fig. 2, A). Small or large empty spaces, similar to incipient serous bursae observed in other anatomic regions, could frequently be found (Fig. 3, B). The rounded appearance, sometimes observed, of these empty spaces, was suggestive of the presence inside of pressurized fluid. There was no leucocytic infiltration on any studied biopsy specimen. Few vessels could be observed.
These alterations were not found in the synovium taken from patients without CTS (Fig. 1). We have attempted to classify the histologic lesions in three grades as follows: grade I: isolated synovial fibrous hypertrophy; grade II: fibrous hypertrophy with localized necrotic areas; grade III: fibrous hypertrophy, with localized necrotic areas and empty spaces similar to serous bursae. We found in our series 4% of grade I, 50% of grade II, and 46% of grade III histologic lesions. There was no statistical difference between the clinical findings in patients with grades II and III histologic lesions (Table I). However, it should be noted that in the cases with thenar atrophy, the histologic lesions were always of grade III.
Discussion Carpal tunnel syndrome comprises a constellation of signs and symptoms caused by compression of the median nerve at the wrist. The effects of compression on the nerve are now well known.20, 23-31However, the actual cause of this phenomenon in the idiopathic CTS is not well understood. Wick catheter recordings of the preoperative pressure in the carpal tunnel have confirmed that the median nerve was subjected to abnormal high pressures in cases of idiopathic carpal tunnel syndromes.“. 32Extension or flexion of the wrist increases the local pressure even more.33 In the absence of any other cause of nerve compression, the elevated pressure
Vol. lSA, No. 3 May 1990
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499
Fig. 2. A-B, A 37-year-old woman seen initially with an idiopathic bilateral carpal tunnel syndrome and associated trigger fingers. A, Histology of the flexor synovium. A diffuse necrosis is shown. Beside the necrotic areas, the surviving cells are disposed in small clusters. (Magnification X 1000.) B, Histology of the Al annular pulley at the level of a trigger finger. The collagen is fragmented in eosinophilic debris. The remaining cells are disposed in clusters with chondroblastic aspect (chondroid metaplasia). (Magnification x 640.)
can only be related to a reduced carpal tunnel volume, to some thickening of the flexor retinaculum, or to an hypertrophy of the synovium of the nine flexor tendons passing with the median nerve through the carpal tunnel. Computed tomography (CT) studies have demonstrated that the carpal tunnel is smaller in women compared with men. 34 This might explain the elevated frequency of the disease in women. The carpal tunnel has also been shown to be smaller in women with idiopathic CTS, as compared with unaffected womenNr 35; this bony stenosis seems to be inherited rather than acquired . 33-35 It has been suggested that idiopathic CTS resulted from thickening of the flexor retinaculum, with
compression of the median nerve. However, Tanzer, measuring the thickness of the flexor retinaculum, during operative decompression of the carpal tunnel in patients with median nerve compression at the wrist, and in cadavers, did not find any difference between the two groups.33, 34 Lin et al.36 did not observe any difference in the histologic structure, or in the biomechanical behavior of the carpal palmar ligament, between a group of patients with CTS and a control group. In most cases of idiopathic CTS, there is an obvious cloudy white, nontransparent hypertrophy of the synovium of the flexor tendons. This hypertrophy is usually believed to be related to a nonspecific flexor tenosynovitis. However, our histologic study could not demonstrate any evidence of inflammatory lesions in
500
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The Journal of HAND SURGERY
Fig. 3. A-B, A 40-year-old woman seen initially with a bilateral idiopathic carpal tunnel syrldrome. Histology of the flexor synovium. A, A necrotic area is shown (arrows). (Magnification x 417). B, Empty spaces, suggesting incipient serous bursae, are observed beside a necrotic area . Wagnification X417.)
the synovium. We found no case of lymphocytic infiltration as reported by L1uch,37 Wilhelm et al. ,I8 or by Faithful1 et a1.38in some patients. In the series reported by these last authors, as in our series, most of the patients had no histologic sign of synovitis. Arlet et a1.39reported histologic lesions similar to our findings in a series of nine “primary” carpal tunnel syndromes. Ellis et al.“O also reported “edema and fibrous tissue proliferation in the subendothelial layers of the synovia,” which they believed to be a sequela of deficiency of vitamin B6. Furthermore, if the hypertrophy of the synovium was related to an inflammatory reaction, one would expect to observe simultaneous alterations of the laboratory inflammatory tests. The histologic lesions described in our study are typical of a connective tissue undergoing degeneration under repeated mechanical stresses. Similar pathologic findings may be found in serous bursae, for example at the site of a hallux valgus deformity of the foot, or
around an intermetatarsal nerve during Morton’s disease (Fig. 5). Identical histologic lesions are found in the proximal annular pulley in cases of trigger finger (Fig. 2, B), or in the synovium around the extensor tendons in tendon entrapments at this level. Our hypothesis is that, after an initial mechanical stress of the synovium of the flexor tendons, a vicious cycle is created: the mechanical stresses and the continuous tendon friction in the eventually stenosed carpal tunnel cause some damage to the synovium. Since the synovial cells are relatively undifferentiated, synovial tissue is capable of rapid repair,41 with formation of a scar-type synovial hypertrophy. The vicious cycle arises because such hypertrophy occurs in a restricted anatomical space, and thus enhances the friction and the mechanical stresses. The necrotic areas, where vascuoles may secondarily be observed, could be related to direct mechanical stresses, or to some degree of local ischemia, as reported by L1uch.37 The necrotic areas
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Idiopathic CTS
Fig. 4. A-B, An 81-year-old man with a long-standing history of bilateral carpal tunnel syndrome. The histology of the flexor synovium shows fragmentation of the collagen in rounded corpuscules (“rice degeneration”). The lesions are expanded by edema. A, Magnification X 167. B, Magnification X4000.
Fig. 5. A 41-year-old woman seen initially with Morton’s disease. Along the injured nerve (not shown on this figure), localized necrosis of the connective tissue is formed (arrows), suggestive of mechanical lesions similar to those observed in the synovium of patients with idiopathic carpal tunnel syndrome (Compare with Fig. 3). (Magnification x 640.)
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are expanded by edema fluid, which is in equilibrium with the extracellular fluid, as there are no intracellular bridges connecting the pseudoepithelial synovium border.42 Several facts corroborate our hypothesis: 1. Epidemiologic studies have demonstrated the role of repeated mechanical stresses in the development of cumulative trauma disorders of the upper extremity such as tenosynovitis, bursitis, or CTS. Various morbidity patterns are associated with repeated exertions and certain job-related factors.7, 9, 33,43-56Symptoms are often produced or aggravated by a sudden increase in manual activity.33 Experimental studies done by Rais showed similar tissue changes in the rabbit induced by over exercising the hind limb. 57Biomechanical studies have confirmed the presence of significant stresses at the tendon-tendon sheath and retinacular interfaces at the wrist and hand.23, 43,46 2. The mechanical lesions observed in the synovium are not only responsible for the compression of the median nerve, they are the cause of the associated complains of stiffness of the fingers. This explains the high frequency of associated trigger fingers (29% in the present series) 3. Edema probably plays a major role in the pathogenesis of the disease, aggravating the swelling of the synovium, and therefore aggravating the friction in the carpal tunnel. The fluid retention favored by pregnancy or menopause could explain the frequency of the disease in pregnant or in premenopausal women. 4. The vicious cycle may be broken by a single increase in the volume of the carpal tunnel (simple division of the flexor retinaculum), by lowering the mechanical stresses (spontaneous improvement during the holidays, or if a local splint is applied”), by systemic treatment with chlorothiazide,58 or by local injection of corticosteroids . Conclusion In all the patients studied, median nerve compression in idiopathic CTS was related to a fibrous hypertrophy of the flexor tendon synovium. Histologic findings were suggestive of repeated mechanical stresses, inducing local necrosis with edema and collagen fragmentation. Our hypothesis is that the syndrome results from a vicious cycle: After an initial episode of mechanical stress, synovium swelling, occurring in a restricted anatomical space, enhances frictions and thus increases further swelling and fibrous hyperplasia. A single decompressive surgical operation, increasing the available volume in the carpal tunnel for the nerve and the nine flexor tendons, may suppress the chronic nerve compression.
REFERENCES 1. Ditmars DM, Houin HP. Carpal tunnel syndrome.
Hand
Clinics 1986;2:525-32. 2. Dorwart BB. Carpal tunnel syndrome: a review. Semin Arthritis Rheum 1984;14:134-40. 3. Johnston AW. Acroparaesthesiae and acromegaly. Br Med J 1960;1:1616-8. 4. Morelli E, Pajardi G, Saporiti E. Le syndrome du canal carpien. 1351 cas op&es. J Chir 1986;123:407-10. 5. Phalen GS, Kendrick JI. Compression neuropathy of the median nerve in the carpal tunnel. JAMA 1957;164:52430. 6. Phillips RS. Carpal tunnel syndrome as a manifestation of systemic disease. Ann Rheum Dis 1967;26:59-63. 7. Silverstein BA, Fine LJ, Armstrong TJ. Occupational factors and carpal tunnel syndrome. Am J Ind Med 1987;11:343-58. 8. Phalen GS. The carpal-tunnel syndrome. Seventeen years’ experience in diagnosis and treatment of 654 hands. J Bone Joint Surg 1966;481\:21 l-28. 9. Phalen GS. The carpal tunnel syndrome. Clinical evaluation of 598 hands. Clin Orthop 1972;83:29-40. 10. Tanzer RC. The carpal tunnel syndrome. Clin Orthop 1959;15:171-9. 11. Chaise F, Witvoet J. Mesures des pressions intra canalaires dam le syndrome du canal carpien idiopathique non deficitaire. Rev Chir Orthop 1984;70:75-8. 12. Conklin JE, White WL. Stenosing tenosynovitis, and its possible relation to the carpal tunnel syndrome. Surg Clin North Am 1960;40:531-40. 13. Harris CM, Tanner E, Goldstein MN, Petee DS. The surgical treatment of the carpal-tunnel syndrome correlated with preoperative nerve-conduction studies. J Bone Joint Surg 1979;61A:93-8. 14. Lister G. The hand. Diagnosis and indications. 2nd ed. London: Churchill Livingstone, 1984:1-389. 15. Nissen KI. Etiology of carpal compression of the median nerve. J Bone Joint Surg 1952;34B,514-5. 16. Robbins H. Anatomical study of the median nerve in the carpal tunnel and etiologies of carpal-tunnel syndrome. J Bone Joint Surg 1963;45A:953-66. 17. Smith EM, Sonstegard DA, Anderson WI-I. Carpal tunnel syndrome: contribution of flexor tendons. Arch Phys Med Rehabil 1977;58:379-85. 18. Wilhelm K, Feldmeier C, Briegel J, Meister P. Genese des Karpaltunnelsyndroms. Pathologisch anatomische Studie. Muench Med Wschr 1982;124:661-2. 19. Yamaguchi DM, Lipscomb PR, Soule EH. Carpal tunnel syndrome. Minn Med 1965;48:22. 20. Gelbennan RH, Pfeffer GB, Galbraith RT, Szabo RM, Rydevik B, Dimick M. Results of treatment of severe carpal-tunnel syndrome without internal neurolysis of the median nerve. J Bone Joint Surg 1987;69A:896-903. 21. Melvin JL, Schuchmann JA, Lanese RR. Diagnostic specificity of motor and sensory nerve conduction variables in the carpal tunnel syndrome. Arch Phys Med Rehabil 1973;54:69-74. 22. Freshwater MF, Arons MS. The effect of various adjuncts
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on the surgical treatment of carpal tunnel syndrome secondary to chronic tenosynovitis. Plast Reconstr Surg 1978;61:93-6. 23. Castelli WA, Evans FG, Diaz-Perez R, Armstrong TJ. Intraneural connective tisue proliferation of the median nerve in carpal tunnel syndrome. Arch Phys Med Rehahil 1980;61:418-22. 24. Curtis RM, Eversmann WW. Internal neurolysis as an adjunct to the treatment of the carpal-tunnel syndrome. J Bone Joint Surg 1973;55A:733-40. 25. Lundborg G. Structure and function of the intraneural microvessels as related to trauma, edema formation, and nerve function. J Bone Joint Surg 1975;57A:938-48. 26. Lundborg G, Myers R, Powell H. Nerve compression injury and increased endoneurial fluid pressure: a “miniature compartment syndrome.” J Neural Neurosurg Psychiatry 1983;46: 1119-24. 27. Neary D, Ochoa J, Gilliat RW. Sub-clinical entrapment neuropathy in man. J Neural Sci 1975;24:283-98. 28. Rydevik B, Lundborg G, Nordborg C. Intraneural tissue reactions induced by internal neurolysis. An experimental study on the blood-nerve barrier, connective tissues and nerve fibres of rabbit tihial nerve. Stand J Plast Reconstr Surg 1976;10:3-8. 29. Rydevik B , Lundborg G. Permeability of intraneural microvessels and perineurium following acute, graded experimental nerve compression. Stand J Plast Reconstr Surg 1977;11:179-87. 30. Rydevik B, Lundborg G, Bagge U. Effects of graded compression on intraneural blood flow. An in vivo study on rabbit tibial nerve. J HANDSURG 1981;6:3-12. 3 1. Sunderland S . The nerve lesion in the carpal tunnel syndrome. J Neurol Neurosurg Psychiatry 1976;39:615-26. 32. Chaise F, Roger B, Laval-Jeantet M, Alhomme P. Exploration tomodensitometrique des modifications anatomiques du poignet entrainees par la section du ligament annulaire ant&ieur. Rev Chir Orthop 1986;72:297-302. 33. Tamer RC. The carpal tunnel syndrome. A clinical and anatomical study. J Bone Joint Surg 1959;41A:626-34. 34. Dekel S, Papaioannou T, Rushworth G, Coates R. Idiopathic carpal tunnel syndrome caused by carpal stenosis. Br Med J 1980;280:1297-99. 35. Gelmers HJ. Primary carpal tunnel stenosis as a cause of entrapment of the median nerve. Acta Neurochir 1981;55:317-20. 36. Lin R, Lin E, Engel J, Bubis JJ. Histo-mechanical aspects of carpal tunnel syndrome. Hand 1983;15:305-9. 37. Lluch A. Thickening of the paratenon of the digital flexor tendons: cause or consequence of the carpal tunnel syndrome? Abstract: The Third Congress of International Federation of Societies for Surgery of the Hand. Tokyo, Japan, November 1986:31. 38. Faithful1 DK, Moir DH, Ireland J. The micropathology of the typical carpal tunnel syndrome. J HAND SURG 1986;11B:131-2. 39. Arlet J, Ficat P, Malbosc J. Les lesions des games tenosynoviales carpiennes dam le syndrome du canal carpien.
Idiopathic CTS
40.
41. 42.
43.
44.
45.
46.
47. 48.
49.
50. 51.
52.
53.
54.
55.
56. 57. 58.
503
Etude histologique de 30 cas op&&. Rev Rhum 1%6;33:194-9. Ellis J, Folkers K, Watanabe T, et al. Clinical results of a cross-over treatment with pyridoxine and placebo of the carpal tunnel syndrome. Am J Clin Nutr 1979; 32:2@40-6. Ham AW. Histology. 6th ed. Philadelphia: Lippincott, 1969. Cohen MJ, Kaplan L. Histology and uhrastructure of the human flexor tendon sheath. J HAND SURG 1987;12A: 25-9. Armstrong TJ, Chaffin DB. Carpal tunnel syndrome and selected personal attributes. J Occup Med 1979;21: 481-6. Birbeck MQ, Beer TC. Occupation in relation to the ;zall tunnel syndrome. Rheumatol Rehabil 1975;14: - . Cannon LJ, Bemacki EJ, Walter SD. Personal and occupational factors associated with carpal tunnel syndrome. J Occup Med 1981;23:255-8. Goldstein SA, Armstrong TJ, Chaffin DB, Matthews LS. Analysis of cumulative strain in tendons and tendon sheaths. J Biomech 1987;20: l-6. Hammer AW. Tenosynovitis. M Record 1934;140:353. Hymovich L, Lindholm M. Hand, wrist and forearm injuries. The result of repetitive motions. J Occup Med 1%6;8:573-7. Lapidus PW, Fenton R. Stenosing tenovaginitis at wrist and fingers. Report of 423 cases in 369 patients with 354 operations. Arch Surg 1952$X475-87. Lapidus PW. Stenosing tenovaginitis. Surg Clin North Am 1953;33:1317-47. Loomis LK. Variations of stenosing tenosynovitis at the radial styloid process. J Bone Joint Surg 1951;33A: 340-6. Miller LF. Stenosing tendovaginitis. A survey of findings and treatment in 49 cases. Indust Med Surg 1950;19: 465-7. Murckart RD. Stenosing tendovaginitis of abductor pollicis longus and extensor pollicis brevis at the radial styloid (de Quervain’s disease). Clin Orthop 1964;33: 201-8. Thompson AR, Plewes LW, Shaw EG. Peritendinitis crepitans and simple tenosynovitis: a clinical study of 544 cases in industry. Br J Ind Med 1951;8:150-60. Wener MH, Metzger WJ, Simon RA. Occupationally acquired vibratory angioedema with secondary carpal tunnel syndrome. Ann Intern Med 1983;98:44-6. Wilson RN, Wilson S. Tenosynovitis in industry. Practitioner 1957;178:612-15. Rais 0. Heparin treatment of peritenomyosis (peritendinitis) crepitans acuta. Acta Chir Stand [SUP@] 1961. Heathfield KWG, Tibbles JAR. Chlorothiazide in treatment of carpal-tunnel syndrome. Br Med J 1961;2: 29-30.
tissue undergoing
degeneration
under repeated
mechanical
stresses.
SURG199O@A:497-503.)
F. Schuind,
MD, M. Ventura, MD, and J. L. Pasteels, MD, PhD, Brussels, Belgium
T
here are numerous clinical settings in which carpal tunnel syndrome occurs. l-7 However, in many patients, no specific cause can be found. The idiopathic form of carpal tunnel syndrome (CTS) occurs more frequently in women, with a peak age range from 40 to 60 years; it is commonly bilateral.8~‘0 Although the disease is very common, its pathophysiology is still not clearly understood. It has been assumed that, in these cases, the median nerve compression is related to a nonspecific synovitis around the flexor tendons. ‘. ‘, *,9, 1o-19This study describes the histologic lesions found in the flexor tendon synovium.
Methods Between February 1985 and August 1987,38 patients had operations to treat 44 carpal tunnel syndromes at the Cliniques Universitaires de Bruxelles, Hopital &asme, by F. S. To study a selected series of “pure” idiopathic CTS , only 2 1 patients fulfilling the following criteria were included in the study: (1) Typical signs and symptoms of carpal tunnel syndrome14; (2) No significant past medical history, i.e., no history of trauma, of hand or wrist infection, of wrist fracture or of other bone or joint wrist injury, no diabetes mellitus, gout, amyloidosis, or any other metabolic or endocrine im-
balances, no history of rheumatoid arthritis or other related disease’; (3) abnormalities in the preoperative electrodiagnostic studies, i.e., prolongation of the distal motor latency beyond 4 msec, or prolongation of the distal sensory latency beyond 3.5 msec14. ‘a. 21; (4) normal standard hand and wrist and carpal tunnel roentgenograms; (5) normal basic laboratory work (sedimentation rate, blood sugar levels, serum uric acid, T3 and T4 levels); negative latex test; (6) at operation, no evident cause of compression of the median nerve in the carpal tunnel, other than thickening of the synovium around the flexor tendons (no vascular or muscular abnormality; no localized tumor); (7) significant postoperative clinical and electrodiagnostic recovery of the median nerveI 22; to be included in the study, the minimum follow-up duration was 6 months; the postoperative electrodiagnostic studies were done 3 months after the surgical procedure. The synovium tissue samples were fixed in Bouin’s solution. The histologic sections were stained by hematoxylin and eosin. All the histologic studies were done by J. L. P. The lesions were compared with samples of synotaken from patients without CTS vium tissue, (Fig. 1). Materials
From the Department of Orthopedics and Traumatology, Hopital Erasme, Cliniques Universitaires de Bruxelles, and the Laboratory of Histology, Brussels School of Medicine, Universite Libre de Bruxelles, Brussels, Belgium. Received for publication July 12, 1989.
Dec. 16, 1988; accepted
in revised form
No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. Reprint requests: F. Schuind, MD, Department of Orthopedics and Traumatology, Hopital Erasme, Cliniques Universitaires de Bruxelles, 808, route de Lemrik, 1070 Brussels, Belgium. 3/l/15628
Twenty-one patients were included in the study; 24 carpal tunnel releases.were done. The average age of the patients was 49 years (range, 32 to 81 years). There were 19 women and 2 men. Results In all biopsy specimens, the histologic findings were similar (Figs. 2 through 4). There was always a fibrous hyperplasia of the synovial membrane, with increased amounts of collagen fibers. The collagen itself was very irregular and disorganized. THEJOURNALOFHANDSURGERY
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498
The Journal of HAND SURGERY
Schu !ind, Ventul pa, and Pasteels
Fig. 1. Normal flexor tendon synovium, taken from a patient without carpal tunnel syndr.ome (the carpal 1:unnel was opened during flexor tendon surgery). (Magnification X 1000.)
Table I. Histologic-clinical
correlation
Histologic grade
Mean age of the patients (yr) Mean preoperative delay of the symptoms (mo) Associated chronic “tendinitis” of the ipsilateral upper limb (%I) Mean distal motor latency (msec) Abductor pollicis brevis paralysis, thenar atrophy (%)
II
53 27 42 6.3 0
III
48 31 36 6.8 33
In more advanced lesions, localized areas with rarefaction, or sometimes with total disappearance of the fibroblasts, could be found (Fig. 2, A, Fig. 3, A, and B). In these necrotic areas, the collagen fibers showed fragmentation in eosinophilic debris, demonstrated by small (diameter, a couple of microns) rounded corpuscules (“rice” degeneration, Fig. 4), or even by a homogeneous necrotic “pap.” Beside these necrotic areas, the surviving cells were sometimes disposed like cords or in small accumulations of rounded cells, similar to chondrocytes (chondroid metaplasia, Fig. 2, A). Small or large empty spaces, similar to incipient serous bursae observed in other anatomic regions, could frequently be found (Fig. 3, B). The rounded appearance, sometimes observed, of these empty spaces, was suggestive of the presence inside of pressurized fluid. There was no leucocytic infiltration on any studied biopsy specimen. Few vessels could be observed.
These alterations were not found in the synovium taken from patients without CTS (Fig. 1). We have attempted to classify the histologic lesions in three grades as follows: grade I: isolated synovial fibrous hypertrophy; grade II: fibrous hypertrophy with localized necrotic areas; grade III: fibrous hypertrophy, with localized necrotic areas and empty spaces similar to serous bursae. We found in our series 4% of grade I, 50% of grade II, and 46% of grade III histologic lesions. There was no statistical difference between the clinical findings in patients with grades II and III histologic lesions (Table I). However, it should be noted that in the cases with thenar atrophy, the histologic lesions were always of grade III.
Discussion Carpal tunnel syndrome comprises a constellation of signs and symptoms caused by compression of the median nerve at the wrist. The effects of compression on the nerve are now well known.20, 23-31However, the actual cause of this phenomenon in the idiopathic CTS is not well understood. Wick catheter recordings of the preoperative pressure in the carpal tunnel have confirmed that the median nerve was subjected to abnormal high pressures in cases of idiopathic carpal tunnel syndromes.“. 32Extension or flexion of the wrist increases the local pressure even more.33 In the absence of any other cause of nerve compression, the elevated pressure
Vol. lSA, No. 3 May 1990
idiopathic CTS
499
Fig. 2. A-B, A 37-year-old woman seen initially with an idiopathic bilateral carpal tunnel syndrome and associated trigger fingers. A, Histology of the flexor synovium. A diffuse necrosis is shown. Beside the necrotic areas, the surviving cells are disposed in small clusters. (Magnification X 1000.) B, Histology of the Al annular pulley at the level of a trigger finger. The collagen is fragmented in eosinophilic debris. The remaining cells are disposed in clusters with chondroblastic aspect (chondroid metaplasia). (Magnification x 640.)
can only be related to a reduced carpal tunnel volume, to some thickening of the flexor retinaculum, or to an hypertrophy of the synovium of the nine flexor tendons passing with the median nerve through the carpal tunnel. Computed tomography (CT) studies have demonstrated that the carpal tunnel is smaller in women compared with men. 34 This might explain the elevated frequency of the disease in women. The carpal tunnel has also been shown to be smaller in women with idiopathic CTS, as compared with unaffected womenNr 35; this bony stenosis seems to be inherited rather than acquired . 33-35 It has been suggested that idiopathic CTS resulted from thickening of the flexor retinaculum, with
compression of the median nerve. However, Tanzer, measuring the thickness of the flexor retinaculum, during operative decompression of the carpal tunnel in patients with median nerve compression at the wrist, and in cadavers, did not find any difference between the two groups.33, 34 Lin et al.36 did not observe any difference in the histologic structure, or in the biomechanical behavior of the carpal palmar ligament, between a group of patients with CTS and a control group. In most cases of idiopathic CTS, there is an obvious cloudy white, nontransparent hypertrophy of the synovium of the flexor tendons. This hypertrophy is usually believed to be related to a nonspecific flexor tenosynovitis. However, our histologic study could not demonstrate any evidence of inflammatory lesions in
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The Journal of HAND SURGERY
Fig. 3. A-B, A 40-year-old woman seen initially with a bilateral idiopathic carpal tunnel syrldrome. Histology of the flexor synovium. A, A necrotic area is shown (arrows). (Magnification x 417). B, Empty spaces, suggesting incipient serous bursae, are observed beside a necrotic area . Wagnification X417.)
the synovium. We found no case of lymphocytic infiltration as reported by L1uch,37 Wilhelm et al. ,I8 or by Faithful1 et a1.38in some patients. In the series reported by these last authors, as in our series, most of the patients had no histologic sign of synovitis. Arlet et a1.39reported histologic lesions similar to our findings in a series of nine “primary” carpal tunnel syndromes. Ellis et al.“O also reported “edema and fibrous tissue proliferation in the subendothelial layers of the synovia,” which they believed to be a sequela of deficiency of vitamin B6. Furthermore, if the hypertrophy of the synovium was related to an inflammatory reaction, one would expect to observe simultaneous alterations of the laboratory inflammatory tests. The histologic lesions described in our study are typical of a connective tissue undergoing degeneration under repeated mechanical stresses. Similar pathologic findings may be found in serous bursae, for example at the site of a hallux valgus deformity of the foot, or
around an intermetatarsal nerve during Morton’s disease (Fig. 5). Identical histologic lesions are found in the proximal annular pulley in cases of trigger finger (Fig. 2, B), or in the synovium around the extensor tendons in tendon entrapments at this level. Our hypothesis is that, after an initial mechanical stress of the synovium of the flexor tendons, a vicious cycle is created: the mechanical stresses and the continuous tendon friction in the eventually stenosed carpal tunnel cause some damage to the synovium. Since the synovial cells are relatively undifferentiated, synovial tissue is capable of rapid repair,41 with formation of a scar-type synovial hypertrophy. The vicious cycle arises because such hypertrophy occurs in a restricted anatomical space, and thus enhances the friction and the mechanical stresses. The necrotic areas, where vascuoles may secondarily be observed, could be related to direct mechanical stresses, or to some degree of local ischemia, as reported by L1uch.37 The necrotic areas
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Idiopathic CTS
Fig. 4. A-B, An 81-year-old man with a long-standing history of bilateral carpal tunnel syndrome. The histology of the flexor synovium shows fragmentation of the collagen in rounded corpuscules (“rice degeneration”). The lesions are expanded by edema. A, Magnification X 167. B, Magnification X4000.
Fig. 5. A 41-year-old woman seen initially with Morton’s disease. Along the injured nerve (not shown on this figure), localized necrosis of the connective tissue is formed (arrows), suggestive of mechanical lesions similar to those observed in the synovium of patients with idiopathic carpal tunnel syndrome (Compare with Fig. 3). (Magnification x 640.)
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are expanded by edema fluid, which is in equilibrium with the extracellular fluid, as there are no intracellular bridges connecting the pseudoepithelial synovium border.42 Several facts corroborate our hypothesis: 1. Epidemiologic studies have demonstrated the role of repeated mechanical stresses in the development of cumulative trauma disorders of the upper extremity such as tenosynovitis, bursitis, or CTS. Various morbidity patterns are associated with repeated exertions and certain job-related factors.7, 9, 33,43-56Symptoms are often produced or aggravated by a sudden increase in manual activity.33 Experimental studies done by Rais showed similar tissue changes in the rabbit induced by over exercising the hind limb. 57Biomechanical studies have confirmed the presence of significant stresses at the tendon-tendon sheath and retinacular interfaces at the wrist and hand.23, 43,46 2. The mechanical lesions observed in the synovium are not only responsible for the compression of the median nerve, they are the cause of the associated complains of stiffness of the fingers. This explains the high frequency of associated trigger fingers (29% in the present series) 3. Edema probably plays a major role in the pathogenesis of the disease, aggravating the swelling of the synovium, and therefore aggravating the friction in the carpal tunnel. The fluid retention favored by pregnancy or menopause could explain the frequency of the disease in pregnant or in premenopausal women. 4. The vicious cycle may be broken by a single increase in the volume of the carpal tunnel (simple division of the flexor retinaculum), by lowering the mechanical stresses (spontaneous improvement during the holidays, or if a local splint is applied”), by systemic treatment with chlorothiazide,58 or by local injection of corticosteroids . Conclusion In all the patients studied, median nerve compression in idiopathic CTS was related to a fibrous hypertrophy of the flexor tendon synovium. Histologic findings were suggestive of repeated mechanical stresses, inducing local necrosis with edema and collagen fragmentation. Our hypothesis is that the syndrome results from a vicious cycle: After an initial episode of mechanical stress, synovium swelling, occurring in a restricted anatomical space, enhances frictions and thus increases further swelling and fibrous hyperplasia. A single decompressive surgical operation, increasing the available volume in the carpal tunnel for the nerve and the nine flexor tendons, may suppress the chronic nerve compression.
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