Key words ankylosing spondylitis - non-radiographic axial spondyloarthritis - neck muscle -
ultrasound - axial spondyloarthritis
Schlüsselwörter Axiale Spondyloarthritis - Spondylitis ankylosans - nicht röntgenologische axiale
Spondyloarthritis - Ultraschall - Nackenmuskulatur
Introduction
Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that mainly affects
the spine and sacroiliac joints. AxSpA is classified as ankylosing spondylitis
(established AS) with sacroiliac joint involvement fulfilling the modified New York
criteria (mNY criteria) and non-radiographic axial spondyloarthritis (nr-axSpA)
without the sacroiliac joint involvement fulfilling mNY criteria detected by
conventional radiography [1 ]. In both AS and
nr-axSpA patients, symptoms such as the neck, low back, and gluteal pain, morning
stiffness, difficulty in movement, fatigue, and sleep disturbance are observed, and
these symptoms cause a decrease in quality of life [2 ].
In axSpa, vertebral bodies, intervertebral discs, and paravertebral muscles of the
spine undergo structural changes due to chronic inflammation. During the disease,
sclerosis in the apophyseal joints, erosion and reactive sclerosis in the vertebral
body, calcification in the interspinal ligaments, and intervertebral disc
pathologies are observed. Atrophic changes occur in the paravertebral muscles due
to
chronic changes in the spine and limitation of movement, leading to impairment and
disability in patients’ activities of daily living [2 ]
[3 ]. In
a study by Zhang et al., it was shown that the ratio of muscle fiber area to
collagen fibril area in paraspinal muscle tissues decreased significantly in the
histopathological examination of paraspinal muscles in patients with AS [4 ].
It is hypothesized that patients with AxSpA may also experience changes in the
cervical paravertebral muscle structure due to pain, spinal inflammation, limitation
of movement, and increased neck flexion. To our knowledge, there is no study in the
literature evaluating cervical paraspinal muscle (multifidus, semispinalis cervicis,
semispinalis capitis, splenius capitis, and trapezius) thickness in patients with
axSpA.
This study examines the neck extensor muscle thicknesses of patients with AS and
nr-axSpA by comparing them with healthy volunteers. It also aims to evaluate the
relationship between muscle thickness and disease activity, functional parameters,
neck disability, and quality of life.
Methods
Study Design and Participation
A cross-sectional design was made to compare the ultrasound measurements of neck
extensor muscle thickness of patients with AS, with nr-axSpA, with healthy
participants. Patients meeting ASAS criteria for AxSpA were enrolled to the
study [5 ]. Among these patients, patients
who met the modified New York criteria were classified as AS and the other
patients as nr-axSpA [6 ]. Thirty patients
with AS and 30 patients with nr-AxSpA who were admitted to Kastamonu
Rehabilitation Center Hospital Physical Medicine and Rehabilitation outpatient
clinic , were included to the study consecutively [7 ]. Thirty healthy participants matched for
age, sex, and Body Mass Index (BMI) were included as control group of the study.
Patients who had trauma or spine surgery, inflammatory diseases other than AS
and nr-axSpA, cervical spondylosis, cervical disc herniation, and a history of
malignancy were excluded. The healthy group consisted of individuals who did not
have chronic neck pain and were not diagnosed with any additional disease that
could cause neck pain. The study was approved by the Ethics Committee of
Kastamonu Training and Research Hospital
(2020-KAEK-143–53/25.02.2021). The study was conducted in
accordance with the Helsinki Declaration. Written informed consent was obtained
from all participants.
Clinical Assessment
Demographic and clinical data such as age, gender, and BMI of all participants in
the study were recorded. Symptom duration, sacroiliac X-ray, and laboratory
findings of patients with axSpA were also examined.
In all patients with axSpA, the Bath Ankylosing Spondylitis Disease Activity
Index (BASDAI) [8 ] for disease activity,
the Bath Ankylosing Spondylitis Functional Index (BASFI) [9 ] for functional status, the Bath
Ankylosing Spondylitis Metrology Index (BASMI) for spinal mobility [10 ] Ankylosing spondylitis Quality of Life
(AsQoL) scale [11 ] for quality of life and
Neck Disability Index (NDI) for neck disability [12 ] were applied.
Ultrasound Measurement
Sonographic evaluations of the neck extensor muscles of the participants were
performed with a 12 MHz linear probe (GE Logic BT12, GE Healthcare) by
the same physician with ten years of US experience and who did not know in which
group the participants were. The fourth cervical (C4) vertebral process was
chosen as the US imaging level, similar to the protocol applied in a study
evaluating the muscle thickness of the neck extensor muscles [13 ]. This level also was used in a study by
Valera-Calero et al., that evaluated the cervical multifidus muscle morphology
from the C4 level in healthy individuals [14 ]. The spinous process at the C4 level was determined by US-guided
palpation and marked with an indelible marker pen in the prone position. After
identification, each participant was seated upright in a chair with arms on
their legs, and their head and neck were placed in a neutral position. The probe
was placed transversely over the C4 spinous process and slid laterally until the
echogenic vertebral lamina was clearly defined. The thickness of the multifidus,
semispinalis capitis, semispinalis cervicis, splenius capitis, and trapezius
muscles were measured bilaterally by determining the maximum distance between
the fascial borders of each muscle when the muscles were at rest, and the
average of the muscle thicknesses was recorded ([Fig. 1 ]).
Fig. 1 Ultrasound image for cervical extensor muscle thickness
measurements.
To test the intra-rater reliability, the same physician performed initial
sonographic muscle thickness measurements in 30 healthy individuals according to
the study methodology and repeated them ten days later.
Statistical Analysis
The study population was determined as 81 using the G-power program by taking
impact size 0.355 (based on similar study results) alpha=0.05, power
(1-beta)=0.80 at a confidence level of 95%. A total of 90
patients were included in the study, considering a dropout rate of
25%.
Statistical analysis was performed using the 23.0 SPSS (IBM, Armonk, NY, USA)
statistical package program. In descriptive statistics, the number (%)
was given for discrete variables, and mean±standard deviation or median
(per 25–75) for continuous variables. Compliance of the data with normal
distribution was evaluated with the Kolmogorov-Smirnov test and histogram. The
Chi-square test was used for discrete variables to compare the differences
between groups. Student t-test was used for pairwise comparison between groups
with normal distribution, and Mann-Whitney U test was used for pairwise
comparison between groups of data not conforming to normal distribution. One-way
ANOVA was used to compare the three groups with normal distribution, and the
Tukey test was used as a posthoc test to compare statistically significant
parameters. Spearman correlation analysis was performed for abnormally
distributed data. Whether the correlation coefficient calculated by the
correlation analysis was statistically significant was tested with the
“determination coefficient” (0.01 and 0.05). The significance
level was accepted as p<0.05. The kappa score determined Intra-rater
reliability.
Results
The groups’ mean ages were 42.36±10.0 in AS group, 38.13±7.94
in the nr-axSpA group, and 39.06±8.25 in the healthy group. While there were
11 women and 19 men in the AS group, there were 14 women and 16 men in the nr-axSpA
group and healthy group. There was no statistical difference between the three
groups regarding age, gender, and BMI (respectively; p=0.152,
p=0.665, p=0.673); and similar disease activity (BASDAI
scores>4) were found between patients with AS and nr-axSpA
(p=0.152). A statistically significant difference was found between the AS
and nr-axSpA groups in terms of duration of symptoms, BASFI, BASMI, ASQoL, NDI, CRP,
right and left sacroiliac grades (p=0.006, p=0.012, p=0.045,
p=0.038, p=0.005, p=0.023, p<0.001,
p<0.001). The demographic and clinical characteristics of the participants
are given in [Table 1 ].
Table 1 Demographic and clinical characteristics of the
participants.
AS Group (n=30)
nr-axSpA Grubu (n=30)
Healthy Group (n=30)
p-value
Age (years)
42.36±10.0
38.13±7.94
39.06±8.25
0.152
Gender (F/M), n (%)
11/19 (36.7/63.3)
14/16 (46.7/53.3)
14/16 (46.7/53.3)
0.665
BMI (kg/m2)
27.93±4.87
27.47±4.08
26.86±5.01
0.673
Duration of symptoms (month)
96 (48–180)
60 (22.5–99)
0.006
BASDAI (>4), n (%)
24 (80)
19 (63.3)
0.152
BASFI
4.35 (1.90–6.73)
1.95 (0.48–3.68)
0.012
BASMI
0.5 (0–2.25)
0 (0–1.0)
0.045
ASQoL
12.0 (9.75–14)
9.0 (5.0–12.0)
0.038
Neck Disability Index
17.5 (11.0–26.25)
11.0 (3.0–18.25)
0.005
CRP
12.0 (2.5–19.5)
4.0 (1.87–7.47)
0.023
Right sacroiliac grade
3.5 (3.0–4.0)
1.0 (1.0–2.0)
<0.001
Left sacroiliac grade
3.0 (3.0–4.0)
1.0 (0.75–1.0)
<0.001
AS: Ankylosing spondylitis; nr-axSpA: non-radiographic axial
spondyloarthritis; F: female; M: male; BMI: Body Mass Index;
(mean±standard deviation; n (%); median (per 25–75)
p<0.05 considered statistically significant).
When the patients’ multifidus, semispinalis capitis, semispinalis cervicis,
and splenius capitis muscle thicknesses were compared between the AS, nr-axSpA and
healthy groups, there was a statistically significant difference (p<0.001
p=0.008, p<0.001, p=0.020, respectively). When the
statistically significant results were compared posthoc, there was a statistically
significant difference between the AS and nr-axSpA groups in the multifidus,
semispinalis capitis muscles (respectively, p=0.012, p=0.016).
However, no statistical difference was found between the semispinalis cervicis and
splenius capitis (respectively, p=0.965, p=0.325). Significant
differences were found in the multifidus, semispinalis capitis, semispinalis
cervicis, and splenius capitis muscles when the AS and healthy controls were
compared ( respectively, p<0.001, p=0.021, p<0.001,
p=0.015) . In the nr-axSpA and healthy groups comparison, there was a
statistical difference in the semispinalis cervicis muscle, but no statistical
difference was found in the multifidus, semispinalis capitis, and splenius capitis
muscles (respectively, p=0.001, p=0.222, p=0.992,
p=0.339). No statistical difference was found when the trapezius muscle
thickness was compared between the groups (p=0.070) ([Table 2 ]).
Table 2 Comparison of neck extensor muscle thickness between
groups.
AS Group (n=30)
nr-axSpA Group (n=30)
Healthy Group (n=30)
p-value
Multifidus (cm)
1.31±0.15bc
1.42±0.16a
1.49±0.14a
<0.001
Semispinalis Capitis (cm)
0.54±0.09bc
0.62±0.11a
0.61±0.12a
0.008
Semispinalis Cervicis (cm)
0.46±0.10c
0.47±0.09c
0.57±0.11ab
<0.001
Splenius Capitis (cm)
0.35±0.07c
0.38±0.10
0.41±0.09a
0.020
Trapezius (cm)
0.15±0.03
0.16±0.04
0.17±0.03
0.070
AS: Ankylosing spondylitis; nr-axSpA: non-radiographic axial
spondyloarthritis. a: Indicates the group that differs from the AS group. b:
b: indicates the group that differs from the nr-axSpA group. c: Indicates
the group that differs from the healthy group.
Kappa scores were determined as 0.861 for multifidus, 0.790 for semispinalis capitis,
0.722 for semispinalis cervicis, 0.679 for splenius capitis, and 0.741 for trapezius
muscle to assess intra-rater reliability.
The results of the correlation analysis between neck extensor muscle thickness
(multifidus, semispinalis capitis, semispinalis cervicis, splenius capitis, and
trapezius) and age, BMI, symptom duration, BASDAI, BASFI, BASMI, AsQoL, NDI, CRP,
right and left sacroiliac grade of 60 patients diagnosed with axial SpA (AS,
nr-axSpA) are shown in [Table 3 ].
Table 3 Correlation analysis between neck extensor muscle
thicknesses and parameters in patients with axial SpA.
Multifidus
Sscapitis
SSservicis
SPC
Trapez
Age
-,464**
-,520**
-,261*
-,268*
-0.060
BMI
-.243
.003
.197
.040
-.016
Duration of symptoms
-.123
-.151
.042
.030
-.068
BASDAI
-,428**
-0.223
-,346**
-,353**
-0.162
BASFI
-.243
-.075
-.150
-.195
-,262*
BASMI
-.067
-.039
.129
-.165
.091
AsQol
-,335**
-0.071
-0.196
-,392**
-0.113
Neck Disability Index
-,324*
-,260*
-0.239
-,285*
-0.253
CRP
-.094
.051
.019
-.198
-.011
Right sacroiliac grade
-.210
-,306*
.044
-.071
-.082
Left sacroiliac grade
-.168
-.157
.093
-.100
-.037
*: p<0.05; **: p<0.001. BMI: Body
Mass Index. Spearman correlation analysis was performed and denoted as
rho.
Discussion
To our knowledge and based on our detailed research in the literature, this is the
first study to evaluate neck extensor muscle thickness by ultrasonography in
patients with axSpA. As a result of the study, multifidus, semispinalis capitis,
semispinalis cervicis, and splenius capitis muscle thicknesses were decreased in AS
patients, and semispinalis cervicis muscle thicknesses were decreased in nr-axSpA
patients compared to the healthy group. In addition, there was a significant
negative correlation between neck extensor muscle thickness and age, disease
activity index, neck disability index, and quality of life in patients with
axSpA.
Cervical extensor paraspinal muscles play an important role in stabilizing and moving
the cervical spine in the neck. They help the lateral flexion of the spine to the
same side when contracted unilaterally and the extension movement of the spine when
contracted bilaterally. Structural and morphological changes in the muscles cause
early symptoms such as pain, stiffness, and posture disorder. In cases such as
persistent pain and inflammation and phobia of exercises due to pain, limitation of
movement and muscle atrophy can occur, which causes the pain to become chronic and
limiting the person’s daily living activities. In a study conducted on
office workers with unilateral chronic neck pain, it was found that semispinalis
capitis muscle thickness was decreased compared to the control group evaluated by
ultrasonography [15 ]. In a study by Penas et
al., it was found that the cross-sectional area of the multifidus muscle was lower
in women with chronic neck pain compared to the control group [16 ]. Goodarzi et al. found a significant
difference in the participants’ resting multifidus, semispinalis cervicis,
semispinalis capitis, splenius capitis, and trapezius muscle thicknesses with
forward head posture compared to those with normal head posture [13 ]. These studies in the literature show the
relationship between muscle thickness and pain/posture disorder. Similarly,
in the present study, when compared to the control group, the thickness of the
muscles other than the trapezius was significantly lower in the AS group. In the
nr-axSpa group, only the semispinalis cervicis muscle thickness was significantly
reduced compared to the control group. The major decrease in muscle thickness in the
AS group is thought to be since chronic inflammation, immobilization, and postural
changes are more established over time.
There is no study in the literature evaluating paraspinal muscles in the neck in
AxSpA patients. The number of studies evaluating the lumbar paraspinal muscles is
few [17 ]
[18 ]. Akgul et al. evaluated the cross-sectional area and fat infiltration
of the paraspinal muscles (multifidus, erector spinae, psoas) in patients with
nr-axSpA and established AS with MRI. They found that the paraspinal
muscles’ cross-sectional area was similar between the groups, and patients
with AS had higher degrees of fat infiltration than patients with nr-axSpA [17 ]. Resorlu et al. compared multifidus and
erector spinae muscle cross-sectional areas and fatty degenerations in the lumbar
region between AS patients and the control group. Paravertebral muscle
cross-sectional areas and fatty degeneration were higher in AS patients compared to
the control group.
Additionally, a negative correlation was observed between the cross-sectional area
of
paravertebral muscles and the duration of the disease [18 ]. Although the anatomy of the cervical and
lumbar spine regions and their involvement in the axSpA are different, in the
present study in which the cervical paraspinal muscles were evaluated, findings
consistent with the studies performed in the lumbar region were found. A
statistically significant difference was found in paravertebral muscle thickness
between AS, nr-axSpA, and control groups. Moreover, there was a significant negative
correlation between disease duration and muscle thickness.
Magnetic resonance imaging, computed tomography, and ultrasonography are frequently
used in evaluating the cervical spine and paraspinal muscles. Ultrasound is
frequently preferred recently in evaluating the musculoskeletal system because it
does not contain radiation, is inexpensive, and is easily accessible. However, it
is
known that it depends on the person’s experience doing it [19 ]. A systemic review emphasized that
ultrasonography is a reliable and valid method for cervical muscle evaluation [20 ]. In a study by Nagai et al. in which the
gender differences in neck flexor and extensor muscle thicknesses were compared with
ultrasound, they did not find a statistical difference between men and women in
cervical extensor muscle thicknesses. In addition, intra-class correlation
coefficient (ICC) intra-rater reliability was 0.852 [21 ]. In this study, the ICC was found to be between 0.679 and 0.861. The
findings show that ultrasound is an effective diagnostic method for evaluating neck
paravertebral muscle thickness in axSpa patients.
In diseases with chronic neck pain, muscle strength and volume decrease over time
due
to various reasons, and this situation becomes a vicious circle with more pain and
stiffness. Therefore, neck exercises are important in preserving the existing muscle
volume and stabilizing the spine in diseases that tend to become chronic. Kashfi et
al. compared the effectiveness of general exercise and deep neck muscle-specific
neck exercises in patients with chronic neck pain. While both exercise treatments
are effective, the importance of a specific exercise program for deep neck muscles
has been emphasized both on pain and to reduce chronic complications [22 ]. Exercise plays a vital role in the
rehabilitation process of axSpA patients. Regular exercise is vital in this patient
group to increase mobility, endurance, and strength, reduce pain and increase the
quality of life of the patients [23 ]. A study
by Öztürk et al. concluded that atrophy occurs in the paravertebral
muscles due to increased thoracic kyphosis, mechanical stress and inflammatory pain,
and immobilization in patients with AS and nr-axSpA [24 ]. The present study determined that neck muscle thicknesses decreased
in patients with AS, nr-axSpA compared to the control group. The importance of
exercise therapy is emphasized in patients with established AS and in patients who
have not yet completed their evolution and whose disease duration is short.
Therefore, planning a specific exercise program for the paravertebral muscles in the
early period in patients with axSpA will positively affect possible pain,
disability, and quality of life.
The correlation analysis determined a negative correlation between muscle thickness
and age, BASDAI, AsQol, NDI scores. In addition, a negative correlation was found
between trapezius muscle thickness and BASFI and sacroiliac joint grade and SSC.
This explains that as mobility impairment and radiologic progression increase ,
paraspinal muscle involvement is more significant. Since AS and nr-axSpA are chronic
inflammatory processes, we think the relationship between paraspinal muscle
thickness and functional index, quality of life scale, and neck disability index is
bidirectional rather than a cause-effect relationship. For this reason, atrophy in
cervical neck extensors causes increased neck pain, worsening in functional status,
deterioration in the quality of life, and as a result, the chain of the vicious
circle cannot be broken, resulting in a decrease in the thickness of the muscles due
to pain and immobility.
The limitations of the study include evaluating cervical muscle thickness only at
the
C4 level, not using muscle cross-sectional area, and measuring only resting muscle
thickness. The number of our patients was small, which may have caused inadequacy
in
the statistical evaluation of the data. In addition, our study was a cross-sectional
study, so the effects of the patients in the future follow-up are not known.
However, the strength of this study is that it is the first study in which muscle
thickness was compared with ultrasound in both AS and nr-axSpA patients.
Conclusion
In conclusion, neck extensor muscle thicknesses are decreased in patients with AxSpA
compared to healthy individuals, and this situation can be reliably detected by
ultrasound. This study will guide studies that will examine the neck muscles in
detail with large patient groups diagnosed with AxSpA.
