WRIST EXTENSOR MUSCLE PATHOLOGY IN LATERAL EPICONDYLITIS

WRIST EXTENSOR MUSCLE PATHOLOGY IN LATERAL EPICONDYLITIS B.-O. LJUNG, R. L. LIEBER and J. FRIDÉN From the Departments of Hand Surgery, Stockholm Söder Hospital, Stockholm and Sahlgrenska University Hospital, Göteborg, Sweden

The morphology of the extensor carpi radialis brevis (ECRB) muscle was investigated in 20 patients with longstanding lateral epicondylitis. Muscle biopsies were obtained from the proximal or distal portion of the ECRB and analysed by enzyme- and immunohistochemical methods. Morphological abnormalities were significantly more frequent in patients than controls and included moth-eaten fibres, fibre necrosis and signs of muscle fibre regeneration as well as higher percentages of the fasttwitch oxidative (type 2A) fibre type. Changes were equally distributed proximally and distally. It is concluded that these changes, directly or indirectly, may reflect the cumulative effect of mechanical and/or metabolic overload and that decreased muscular performance in patients with lateral epicondylitis may be due to both elbow pain and physical damage to the ECRB muscle. Journal of Hand Surgery (British and European Volume, 1999) 24B: 2: 177–183 The aetiology of lateral epicondylitis (tennis elbow) is poorly understood but there is a general agreement that the extensor carpi radialis brevis (ECRB) muscle and its origin are involved in its pathogenesis. Previous histopathological studies have mainly focused on the origin of the ECRB muscle (Coonrad and Hooper, 1973; Cyriax, 1936; Goldie, 1964; Regan et al, 1992). However, these studies have provided conflicting results. Microruptures in the proximal tendon (Coonrad and Hooper, 1973; Cyriax, 1936), inflammation and granulation tissue but no microruptures (Goldie, 1964) and degenerative changes without signs of inflammation (Regan et al, 1992) have all been reported. The ECRB muscle, its tendinious origin at the lateral epicondyle and its distal tendon may be regarded as a functional unit. In earlier studies we demonstrated that muscle length changes as a function of the wrist and elbow joint angles and have suggested that very high tension levels in the ECRB muscle may be a causative factor in lateral epicondylitis (Fridén and Lieber, 1994; Lieber et al, 1997). In the present study we investigated the morphological status in the ECRB muscle itself in an attempt to further understand the pathophysiology of lateral epicondylitis.

as synovitis in the proximal radioulnar joint, entrapment of the radial nerve, compartment syndrome in the anconeus muscle, arthritis and other joint diseases were excluded by clinical examination. These patients had a mean duration of symptoms of 23.9 months (range, 7–72) and the mean age was 44 years (range, 28–55). Surgery All 20 patients underwent surgery for tennis elbow, ten with lengthening of the distal tendon of the ECRB muscle (Garden, 1961) and ten with release of the proximal muscle origin (Hohmann, 1933). Controls Five healthy volunteers and four autopsy samples from individuals with no history of upper limb disorder and in whom the cause of death would not influence the morphological appearances of ECRB were used. The mean age of these eight men and one woman was 36 years (range, 23–58). Biopsy technique Samples were obtained from a well defined region of the ECRB muscles, 5 and 10 cm distal to the lateral epicondyle. All control biopsies were taken 5 cm distal to the lateral epicondyle. The samples were placed in OCT® embedding medium (Miles Laboratories, Naperville, IL, USA) with their fibres perpendicular to the surface of a piece of cardboard, and frozen in nitrogen-cooled isopentane (–159°C). All the above procedures were approved by the local Committee on the Use of Human Subjects.

PATIENTS AND METHODS Patients Twenty patients, 11 men and nine women, with lateral epicondylitis that had not responded to conservative treatment, were studied. Conservative treatments had included sick leave, instructions to avoid heavy loading and repeated isometric contractions, routine physiotherapy (eccentric exercise, wrist extensor muscle stretching, ultrasound) and one to three steroid injections at the site of maximal point tenderness. All patients had tenderness over the common extensor origin close to the lateral epicondyle and lateral epicondylar pain on resisted extension of the wrist joint. Differential diagnoses such

Tissue processing Eight-micron thick cross sections, taken from the midportion of the tissue blocks, were cut on a cryostat at –25°C (Reichert Jung, 2800 Frigocut, Austria). Serial 177

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sections were stained with haematoxylin and eosin for routine histological analysis, reduced form of nicotineadenine-dinucleotide reductase (NADH), and for myofibrillar ATPase activity after preincubations at pH 4.3, 4.6, and 10.3. Muscle fibres were typed into type 1, 2A, 2B, 2AB and 2C according to a modification of the method of Staron and Pette (1986). Cryosections were stained with antibodies against laminin (rabbit antiserum) to visualize the basal lamina of the fibres (Sanes and Cheney, 1982) and desmin (monoclonal mouse antihuman) to assess the structural integrity of the cytoskeletal network. Antibody binding was visualized by the indirect peroxidase-antiperoxidase technique (Dakopatts, Copenhagen, Denmark). Structural abnormalities were scored using a semiquantitative system (0 = no abnormalities, 1 = occasional i.e., in less than three fascicles per sample, 2 = in every fascicle). Fibre type grouping was defined as fibres of one single type that appeared immediately adjacent to each other, forming a distinct group of one single fibre type (Engel and Franzini-Armstrong, 1994). Statistics Fibre type distribution were compared by using one-way ANOVA. Structural abnormalities were compared by Mann–Whitney U-tests. Significance level was chosen as P < 0.05.

RESULTS Light microscopy Biopsies from the patients demonstrated numerous pathological changes (Fig 1, Table 1). The most frequent changes were an abundance of fibres with an abnormal distribution or loss of NADH stain (motheaten fibres), a variable number of de- and regenerating fibres as evidenced by abnormal desmin staining patterns, and the occurrence of fibre type grouping. These abnormalities were generally scattered within the fascicles and throughout the cross-section of the biopsy. Many fibres were found to be invaded by phagocytes and had various degrees of membrane disruption and total or partial loss of desmin. Abnormalities were more frequent in biopsies taken from patients than from controls. The pathological findings were essentially the same in the proximal and distal portions of the ECRB. Moth-eaten fibres were found in 80% of the patients compared with only 11% in the controls (P < 0.05). Severe or occasional necrosis occurred in 60% of the patients and occasional necrotic fibres in 11% of controls (P < 0.05). Fibre type grouping was observed in 30% of the tennis elbow patients compared to 0% of the controls. Central nuclei that are considered a normal feature of skeletal muscle approaching a musculotendinous insertion were found in both groups.

a Fig 1

Photomicrographs of serial sections of biopsy from the ECRB muscle in patient with lateral epicondylitis. The arrows identify necrotic fibres. (a) Haematoxylin and eosin stain. Necrotic fibres undergoing phagocytosis are indicated.

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b

c Fig 1

(continued) (b) NADH diaphorase. The heavily stained fibres are type 1 fibres. The long arrow shows a fibre with “motheaten” change. (c) ATPase pH 4.3. The dark-stained fibres are type 1 indicating a type 1 predominance.

Fibre type distribution

DISCUSSION

Type 2B fibres were found in only 15% of the biopsies from the patients whereas they were detected in 89% of the controls. Type 2AB fibres were found in no patients but in 44% of the controls. Type 2C fibres were found in 45% of the patients compared with 22% of the controls. In the patients, the percentage of type 2A fibres was greater and the proportions of types 2B and 2AB fibres were significantly smaller than controls (Fig 2). Fibre type distribution was essentially the same proximally and distally along the muscle length.

This study demonstrated pathological changes in ECRB muscle samples from patients with chronic lateral epicondylitis. Although the morphological changes as well as the clinical symptoms varied between subjects, a number of morphological abnormalities were found in all patients. These are likely to reflect mitochondrial redistribution and muscle fibre necrosis, regeneration and conversion of fibre types to more oxidative forms. The changes may have occurred as a response to load or to metabolic conditions or both.

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d

e Fig 1

(continued) (d) ATPase pH 10.3. Light fibres are type 1, dark fibres are type 2. (e) laminin staining outlining the sarcolemma of the muscle fibres.

In a recent study, a biphasic lengthening of the ECRB muscle during progressive elbow flexion was observed (Lieber et al, 1997). This is believed to impose eccentric contractions on the muscle itself. It is known that eccentric muscle actions may result in structural damage to the myofibrillar apparatus (Fridén et al, 1983) and subsequent inflammation (Mishra et al, 1995). Therefore, such cyclic motion could result in chronic muscle inflammation and decreased contractile performance as has been observed in animal (Armstrong et al, 1983; Lieber et al, 1994) and human models (Clarkson et al, 1982; Evans et al, 1986). The high tension levels following eccentric contractions may cause muscle damage, fibre necrosis and regeneration, as described in this study.

Moth-eaten fibres have been described in the trapezius muscle in patients with myalgia in the neck and shoulder region (Larsson et al, 1988; Lindman et al, 1991). However, in studies of the trapezius muscle, moth-eaten cells are frequently also seen in the unaffected side and in healthy volunteers, especially in the upper part of the muscle (Bengtsson et al, 1986; Larsson et al, 1988; Lindman et al, 1991). It has been speculated that these morphological changes are associated with load (Bengtsson et al, 1986) since this portion of the muscle supports the shoulder and is under more or less continuous strain (Bateman, 1978). Heffner and Barron (1978) postulated that moth-eaten cells represent early ischaemia and ragged red fibres more pronounced

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f Fig 1

(continued) (f) desmin. Note the loss of the cytoskeletal protein desmin in the arrowed necrotic fibre groups. Bar = 100 µm.

Table 1—Structural abnormalities in the ECRB muscle in patients with lateral epicondylitis Case Moth eaten fibres

Structural abnormalities Fibre type Central grouping nuclei

Necrosis

Proximal 1 2 3 4 5 6 7 8 9 10 Total score:

1 0 2 1 0 2 0 1 1 1 9

0 0 0 0 1 0 1 1 0 0 3

1 1 1 1 1 1 1 1 1 1 10

0 1 0 0 1 1 1 1 0 1 6

Distal 11 12 13 14 15 16 17 18 19 20 Total score:

1 0 1 1 1 1 1 1 2 1 10

0 0 1 1 0 0 1 0 0 0 3

1 2 1 1 0 1 2 1 1 1 11

0 0 1 1 0 0 2 1 1 2 8

0 0 0 1 0 0 0 0 0 1 P < 0.05

0 0 0 0 0 0 0 0 0 0 ns

1 1 1 1 1 1 1 0 1 8 ns

0 0 0 0 1 0 0 0 0 1 P < 0.05

Control A B C D E F G H I Total score:

P values indicate comparisons between the sum of the proximal and distal total abnormality score and the controls.

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Fig 2

Bar graph showing proportions of ECRB muscle fibre types in patients and controls. The number of individuals exhibiting each fibre type is given above the bars. Values given as mean (SD).

ischaemia. In our study, we found no ragged red fibres which contrasts with the studies of the trapezius muscle where such fibres were present in the affected muscles (Larsson et al, 1988; 1990). Studies of the trapezius muscle have also shown a decreased blood perfusion in association with pain and morphological changes (Larsson et al, 1990). The differences in fibre type distribution between the patients and the controls showed a shift in the patient group from type 2B and type 2AB fibres to the more oxidative, type 2A fibres. A similar change has been demonstrated in patients with intermittent claudication (Hammarsten et al, 1980) and may be an expression of the need for fibres with increased oxidative capacity in a hypoxic environment. A redistribution of mitochondrial enzyme stain (moth-eaten cells) and the loss of fasttwitch type 2 fibres with a conversion to more oxidative forms could indicate an adaptation to a relative ischaemia. Type 2C fibres may be regarded as precursors to other fibre types and/or an expression of fibre regeneration (Dubowitz, 1985; Engel and Franzini-Armstrong, 1994; Nonaka, 1991). In this study, the proportion of type 2C fibres was equal in both groups but there were relatively more individuals in the patient group (9/20 vs 2/9) exhibiting type 2C fibres. This indicates fibre regeneration in the patient group that is reasonable since the proportion of necrotic fibres was significantly increased in this group. Other possible explanations for the changes observed include the effects of reduced use of the affected arm

and damage caused by steroid injections. A relative immobilization may cause atrophy and changes of fibre type distribution but not necrosis. Steroid injections are not likely to cause any damage to the muscle because of the distance between the sites of injection and biopsy. In addition, the injections were given adjacent to the origin of the ECRB tendon, not into the muscle itself. Although we have shown morphological changes in the ECRB muscle in patients with lateral epicondylitis, it is not possible to determine whether the morphological changes represent the primary pathology of tennis elbow or a secondary effect. It is not known whether a painful tendon origin leads to reactive changes in the attached muscle. An insufficient blood supply may lead to decreased contractile properties and an increased vulnerability to high levels of muscular tension. It is also possible that the suggested high levels of tension in the ECRB musculotendinous system cause both muscle damage and mechanically induced pain at the origin. In conclusion, the ECRB muscle shows morphological changes in patients with lateral epicondylitis. We postulate that decreased muscular performance in these patients is associated with both elbow pain and physical damage to the ECRB muscle. Acknowledgements This work was supported by the Swedish Medical Research Council (project no. 11200), the Swedish Work Environment Fund, the Swedish National Centre for Research in Sports, the Swedish Society for Medical Research, Departments of Veteran Affairs and NIH Grant AR40050. We thank Ulla Hedström and Ulrika Sandström for their skilful help with the tissue processing and morphological analyses.

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Received: 19 December 1997 Accepted after revision: 28 August 1998 B-O. Ljung MD, Department of Hand Surgery, Stockholm Söder Hospital, S-118 83 Stockholm, Sweden. E-mail: [email protected] © 1999 The British Society for Surgery of the Hand Article no. jhsb 1998.0178