Download Wrist Extensor Muscle Pathology in Lateral Epicondylits

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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THE JOURNAL OF HAND SURGERY VOL. 24B No. 2 APRIL 1999
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.
MUSCLE MORPHOLOGY IN LATERAL EPICONDYLITIS
179
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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THE JOURNAL OF HAND SURGERY VOL. 24B No. 2 APRIL 1999
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
MUSCLE MORPHOLOGY IN LATERAL EPICONDYLITIS
181
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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THE JOURNAL OF HAND SURGERY VOL. 24B No. 2 APRIL 1999
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.
MUSCLE MORPHOLOGY IN LATERAL EPICONDYLITIS
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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