Does muscle morphology change in chronic neck pain patients? – A systematic review

Abstract

Background:
Neck pain is a common disabling worldwide health problem with a high socio-economic burden. Changes underlying the transition to, or the maintenance of a chronic state are still barely understood. Increasing evidence suggests that morphological muscle changes, including changes in cross-sectional area (CSA) or fatty infiltration, play a role in chronic neck pain. However, a structured overview of the current evidence of morphological changes is lacking.

Objective:
To systematically review the morphological muscle changes in patients with chronic neck pain, including those with whiplash-associated disorders (WAD) and chronic idiopathic neck pain.

Study design & methods:
A systematic review using the PRISMA-guidelines.

Results:
Fourteen of 395 papers were included after extensive screening. Most studies were of moderate methodological quality. A higher CSA was found in all flexor muscles in both patients with WAD and patients with chronic idiopathic neck pain, except for the deeper flexor muscles in patients with chronic idiopathic neck pain. The cervical extensor muscles show an increased CSA at the highest cervical segments in patients with WAD, while most studies in patients with chronic idiopathic neck pain report a decreased CSA in all extensor muscles. Fatty infiltration, which could be accountable for an increased CSA, of both cervical extensors and flexors seems to occur only in patients with WAD.

Conclusion:
Some evidence is available for changes in muscle morphology, however more high quality prospective and cross-sectional research is needed to confirm these changes and to identify potential underlying causes that need yet to be discovered.

Full text

Systematic review
Does muscle morphology change in chronic neck pain patients? eA
systematic review
R. De Pauw
*
, I. Coppieters, J. Kregel, K. De Meulemeester, L. Danneels, B. Cagnie
Ghent University, Department of Rehabilitation Sciences and Physiotherapy, De Pintelaan 185 3B3, 9000 Ghent, Belgium
article info
Article history:
Received 6 May 2015
Received in revised form
23 November 2015
Accepted 29 November 2015
Keywords:
Neck pain
Muscle morphology
Whiplash
Fatty infiltration
Cross-sectional area
abstract
Background: Neck pain is a common disabling worldwide health problem with a high socio-economic
burden. Changes underlying the transition to, or the maintenance of a chronic state are still barely
understood. Increasing evidence suggests that morphological muscle changes, including changes in
cross-sectional area (CSA) or fatty infiltration, play a role in chronic neck pain. However, a structured
overview of the current evidence of morphological changes is lacking.
Objective: To systematically review the morphological muscle changes in patients with chronic neck
pain, including those with whiplash-associated disorders (WAD) and chronic idiopathic neck pain.
Study design &Methods: A systematic review using the PRISMA-guidelines.
Results: Fourteen of 395 papers were included after extensive screening. Most studies were of moderate
methodological quality. A higher CSA was found in all flexor muscles in both patients with WAD and
patients with chronic idiopathic neck pain, except for the deeper flexor muscles in patients with chronic
idiopathic neck pain. The cervical extensor muscles show an increased CSA at the highest cervical seg-
ments in patients with WAD, while most studies in patients with chronic idiopathic neck pain report a
decreased CSA in all extensor muscles. Fatty infiltration, which could be accountable for an increased
CSA, of both cervical extensors and flexors seems to occur only in patients with WAD.
Conclusion: Some evidence is available for changes in muscle morphology, however more high quality
prospective and cross-sectional research is needed to confirm these changes and to identify potential
underlying causes that need yet to be discovered.
©2015 Elsevier Ltd. All rights reserved.
1. Introduction
Neck pain is a common disabling worldwide health problem,
with up to 70% of individuals experiencing an episode in their
lifetime (Fejer et al., 2006). The prevalence of chronic neck pain is
still increasing, which results in a growing socio-economic burden
(Hoy et al., 2010). A better understanding of the pathophysiology
underlying chronic neck pain may therefore be beneficial to opti-
mize treatment options and to decrease the socio-economic costs.
Based on its etiology, chronic neck pain is often divided into
idiopathic and traumatic-induced neck pain. Patients who suffer
from trauma-induced neck pain are often referred to as patients
with whiplash associated disorders (WAD) (Spitzer et al., 1995).
Both are accompanied by a variety of symptoms, and persistence of
these symptoms might be associated with muscle modifications.
An altered muscle function (Falla et al., 2004) as well as changes in
muscle properties (Weber et al., 1993; Sterling et al., 2011; Elliott
et al., 2014), which include cross-sectional area (CSA), and muscle
fibre type, have been reported in both patient-groups. Recent evi-
dence, however, suggests that changes in muscle properties may
differ between patients with idiopathic neck pain compared to
patients with WAD, since the appearance of an increased fatty
infiltration seems to be a unique feature seen in patients with WAD
(Sterling et al., 2011).
Measuring morphological features is possible using Magnetic
Resonance Imaging (MRI) and ultrasonography. With both tech-
niques it is possible to measure CSA accurately and reliably (Hides
et al., 1995; Dupont et al., 20 01). However, quantitative measures of
fatty infiltration are currently only possible using MRI, since this
technique may give an indication of the amount of fat by a
distinction of fat and soft-aqueous tissue signal intensities.
*Corresponding author. Tel.: þ32 9 332 12 19; fax: þ32 9 332 38 11.
E-mail addresses: Robby.DePauw@Ugent.be (R. De Pauw), Iris.Coppieters@
Ugent.be (I. Coppieters), Jeroen.Kregel@Ugent.be (J. Kregel), Kayleigh.
DeMeulemeester@Ugent.be (K. De Meulemeester), Lieven.Danneels@Ugent.be
(L. Danneels), Barbara.Cagnie@Ugent.be (B. Cagnie).
Contents lists available at ScienceDirect
Manual Therapy
journal homepage: www.elsevier.com/math
http://dx.doi.org/10.1016/j.math.2015.11.006
1356-689X/©2015 Elsevier Ltd. All rights reserved.
Manual Therapy xxx (2015) 1e8
Please cite this article in press as: De Pauw R, et al., Does muscle morphology change in chronic neck pain patients? eA systematic review,
Manual Therapy (2015), http://dx.doi.org/10.1016/j.math.2015.11.006

Although research on this topic is increasing, an overview of the
current existing evidence is lacking. The aims of this study are
therefore to synthesise and analyse research papers, which have
investigated the morphological muscle changes in patients with
chronic neck pain, together with analyzing the differences between
patients with idiopathic neck pain and WAD. Furthermore, this
study aims at defining the strength of evidence of each study to
make a conclusion on the appearance of these morphological
changes.
2. Materials and methods
This systematic review follows the PRISMA (Preferred Reporting
Items for Systematic reviews and Meta-Analyses) guidelines
(Moher et al., 2009).
2.1. Eligibility criteria, information sources and search strategy
Potential eligible articles were identified by consulting
the electronic databases Cochrane Libarary (http://www.
cochranelibrary.com), PubMed (http://www.ncbi.nlm.nih.gov/
pubmed) and Web of Science (WoS) (www.webofscience.com)in
September 2014. The search request was executed by R.D.P. under
the supervision of B.C.
The search strategy was based on a combination of Mesh-terms
and free text words derived from the following PICO(S) (Patient,
intervention, Comparison, Outcome, and Study Design) question:
participants (P) had to suffer from neck pain, neck injuries or WAD.
The intervention (I) had to include medical imaging techniques
such as MRI, and ultrasonography. The outcome (O) had to contain
morphological changes in the neck muscles such as CSA, fatty
infiltration or muscle fibres type. Where available, Mesh-terms
were entered with their respective free term. The fully entered
search strategy can be found in Table 1.
Articles had to meet the following inclusion criteria: (1) patients
had to suffer from non-specific idiopathic neck pain or WAD. Papers
reporting on participants suffering from specific pathologies
(e.g. metabolic syndromes, neurologic syndromes or fibromyalgia)
were excluded. (2) Only structural medical imaging techniques
were included. Functional techniques such as functional MRI or
EMG were excluded. (3) The outcome measurement should only
consist of morphological properties of the neck muscles. (4) Only
Dutch, French, and English articles were allowed. (5) Case reports
were excluded. (6) Full-text articles of original research had to
be available. An article was excluded when one of the six
mentioned inclusion criteria was not fulfilled.
First, articles were screened for the inclusion criteria on title and
abstract. All possible eligible articles were retrieved and, secondly,
full-text was screened on meeting the inclusion-criteria.
2.2. Qualification of searchers/raters
Literature was searched and screened by R.D.P. and I.C., both
researchers at Ghent University. Risk of bias was assessed by two
researchers R.D.P., a researcher at Ghent University, and B.C., who
earned a PhD and has experience in the process of a systematic
review.
2.3. Data items and collection
An evidence table was made in which each article was sum-
marized. The author's name, year of publication, patients' charac-
teristics, type of intervention, main results, and level of evidence
were extracted from the included articles.
2.4. Risk of bias in individual studies
Methodological quality was assessed by two independent,
blinded researchers (R.D.P. and B.C.) by a checklist that was derived
from the website of the Dutch Cochrane Centre (http://dcc.
cochrane.org/). As all studies included in this review were
caseecontrol or cohort studies, those checklists were used. The six
items that were assessed for a caseecontrol study included de-
scriptions of the patient group and the control group, selection bias,
exposure, blinded measurement of exposure, and confounders. The
checklist for the assessment of cohort studies included the same six
items supplemented with follow-up period, and description of loss
to follow-up. After rating the selected articles, the results of the two
researchers were compared and differences were analysed. In case
of disagreement, the reviewers screened the paper a second time
and the disparities were discussed until consensus was met.
A level of evidence was given to every study. The highest level of
evidence with a greater strength of the results could be obtained
through systematic reviews/meta-analyses (Level A1) or prospec-
tive cohort trials of sufficient size and follow-up that have
adequately controlled for confounding, and selective follow-up is
sufficiently excluded (Level A2). Cohort studies not meeting the
criteria of level A2 or caseecontrol studies are determined as level
Table 1
Search Strategy with according keywords. Boolean terms (AND and OR) were used to separate the different key words.
P(atients) I(ntervention) O(utcome)
Neck pain OR
WAD OR
Whiplash OR
Whiplash associated disorder OR
Neck injuries
AND Ultrasonography OR
CT OR
MRI OR
Medical imaging OR
Computer tomography OR
Magnetic resonance imaging OR
Echography
AND Muscle atrophy OR
Fatty infiltration OR
Fatty infiltration OR
Morphology OR
Muscle infiltration OR
Muscle morphology OR
Muscle fibre type OR
Muscle changes OR
Neck muscles OR
Muscle hypertrophy OR
Adipose tissue OR
Muscle fibres fast twitch OR
Muscle fibres slow twitch OR
Anatomy OR
Histology OR
Cross-section OR
Muscle type OR
Muscle fibre
R. De Pauw et al. / Manual Therapy xxx (2015) 1e82
Please cite this article in press as: De Pauw R, et al., Does muscle morphology change in chronic neck pain patients? eA systematic review,
Manual Therapy (2015), http://dx.doi.org/10.1016/j.math.2015.11.006

Table 2
Evidence table of the included studies.
Article Population Measurement technique Main results
Control (n) Patient (n)
CSA
Elliott et al. (2008b) 34 females
(age: 27.0 ±5.6 yr;
BMI: 23.0 ±4.44 kg/m
2
)
79 females (age: 29.7 ±7.7 yr;
BMI: 25.1 ±5.73 kg/m
2
);
WAD II -patients with
persisting symptoms
(3 monthse3 year)
MRI (1.5T LX GE &
Sonata 1.5T Magnet)
Multifidus,Semispinalis capitus
and splenius capitis (C3):
WAD >controls.
Semispinalis cervicis (C3, C5, and C6),
and Semispinalis capitus (C6):
WAD <control.
Upper Trapezius or suboccipital
muscles:control ¼WAD.
Elliott et al. (2010)
a
31 females
(age: 27.0 ±5.47 yr;
BMI: 22.8 ±4.62 kg/m
2
)
78 females (age: 29.9 ±7.77 yr;
BMI: 25.2 ±5.74 kg/m
2
);
WAD II-patients with
persisting symptoms
(3 monthse3 year)
MRI (1.5 LX GE &
Sonata 1.5T Magnet)
Longus colli,capitis,and SCM:
WAD >control.
Elliott et al. (2014)
b
34 females
(age: 26.9 ±5.6 yr;
BMI: 23.0 ±4.4 kg/m
2
)
79 females with WAD II
(age: 29.8 ±7.8 yr;
BMI: 25.2 ±5.7 kg/m
2
);
23 females with non-traumatic
idiopathic neck pain
(age: 29.2 ±6.8 yr;
BMI: 23.3 ±4.8 kg/m
2
); patients
with persisting symptoms
(3 monthse3 year)
MRI (1.5 LX GE &
Sonata 1.5T Magnet)
CSA (adjusted for fatty infiltration)
Multifidus (C5eC6), Semispinalis
cervicus (C5eC6), Seminspinalis
capitis, Splenius Capitis (C5eC6),
RCPMaj, and RCPmin: INP <control.
Semispinalis cervicus (C5eC6),
Seminspinalis capitis (C5eC6),
Splenius Capitis (C5eC6), RCPMaj,
and RCPmin: WAD <control.
SCM (C5eC6): INP >WAD >control.
SCM (C2eC3): INP >control.
Multifidus (C5eC6),and Splenius
Capitis (C5eC6):WAD >INP.
Semispinalis cervicus and capitis
(C2eC3):WAD <INP.
Fernandez-de-las-Penas
et al., 2008
20 females
(age: 34 ±5 yr;
body mass: 68.9 ±11.3 kg;
height: 172.5 ±4.2 cm);
20 females (age: 33 ±6;
body mass: 66.8 ±8.4 kg;
height: 170.1 ±6.2 cm);
INP >6 months
Ultrasound Imaging Multifidus:
Patients <Controls
Javanshir et al. (2011) 20 (10 females, 10 males;
age: 30 ±6yr;
BMI: 23.8 ±2.7 kg/m
2
)
20 (10 females, 10 males;
age: 31 ±5yr;
BMI: 23.5 ±3.1 kg/m
2
);
Chronic non-traumatic
mechanical neck
pain >3 months
Ultrasonography Longus colli
Patients <controls (total &
antero-posterior)
Kristjansson (2004) 10 females (31.5 ±11.40 yr;
weight: 67.1 ±6.78 kg;
height: 1.69 ±5.48 m)
10 females (32.5 ±11.76 yr;
70.3 ±10.14 kg;
height: 1.68 ±4.95 m);
Chronic WAD II
Ultrasonography Multifidus (C4)
WAD <control
Matsumoto et al. (2012) 60 (36 males, 25 females;
age: 36.7 ±12.5 yr;
BMI: 22.4 ±3.2 kg/m
2
)
23 (13 males, 10 females;
age: 39.4 ±14.4 yr;
BMI: 23.1 ±3.2 kg/m
2
);
WAD patients at 10 years
follow up
MRI (Signa 1.5 T) Splenius capitis (C4-5,C5-6,C3eC4):NS
Multifidus:Initial &follow eup:
WAD >control
Seminispinalis cervicis and capitis
(C3eC4,Total):Follow-up:
WAD >control
Rezasoltani et al. (2010) 10 females
(age: 32.6 ±6.4 yr;
BMI: 22.0 ±1.9 kg/m
2
)
10 females (age: 37.2 ±6.0 yr;
BMI: 25.4 ±2.0 kg/m
2
);
INP during the last year
Ultrasonography Semispinalis capitus
Patients <controls (total &
antero-posterior dimension
Rezasoltani et al. (2012) 10 females
(age: 32.6 ±6.4 yr;
BMI: 22.0 ±1.9 kg/m
2
)
10 females (age:37.2 ±6.0 yr;
BMI: 25.4 ±2.0 kg/m
2
);
INP >3 months
Ultrasonography Semispinalis capitus
Patients <controls (total &
antero-posterior dimension);
affected size <unaffected size
Ulbrich et al. (2012) None 90 (45 females, 42 males;
age: 37.1 ±14.8 yr;
BMI: 25.17 ±3.40 kg/m
2
);
WAD I or II; Acute (within 48 h
after injury), 3, and 6 months
follow-up.
MRI (Sonata
1.5 T Magnet)
SCM (C4):6m>Acute
RCPMaj,OCI,total dorsal cervical
extensor (C2,C5),semispinalis cervicus
þmultifidus þinterspinales þspinales
(C5):NS
Fatty infiltration
Elliott et al., 2006 34 females
(age: 27.0 ±5.6 yr;
BMI: 23.0 ±4.44 kg/m
2
)
79 females (age: 29.7 ±7.7 yr;
BMI: 25.1 ±5.73 kg/m
2
);
INP (not specified); WAD II-
patients with persisting symptoms
(3 monthse3 year)
MRI (1.5 LX GE &
Sonata 1.5T Magnet)
RCPMaj,RCPmin,Multifidi,Trapezius,
semispinalis capitus and cervicis,and
splenius capitis
WAD >Control; C3 >…>C7
(WAD and control)
Elliott et al. (2008a) 79 females suffering
from WAD
(age: 29.7 ±7.8 yr)
23 females (age: 29.2 ±6.9 yr);
INP >3 months
MRI Suboccipitals (RCPMaj and RCPmin),
multifidus,semispinalis cervicis and
capitis,splenius capitis,and upper
trapezius
WAD >INP
(continued on next page)
R. De Pauw et al. / Manual Therapy xxx (2015) 1e83
Please cite this article in press as: De Pauw R, et al., Does muscle morphology change in chronic neck pain patients? eA systematic review,
Manual Therapy (2015), http://dx.doi.org/10.1016/j.math.2015.11.006

of evidence ‘B’. Since no expert opinions or non-controlled trials
were included, no studies qualified for a level of evidence lower
then B (level D and C respectively). As all studies were cohort
studies not meeting the criteria of level A2 or caseecontrol studies,
the level of evidence for all studies was determined as ‘B’.
A strength of conclusion (ranging from 1 to 4) was calculated for
each cluster of studies reflecting one outcome parameter, and was
placed between brackets in the results section. A strength of
conclusion 1 is given for a study of level A1 or at least two inde-
pendently conducted studies of level A2. A strength of conclusion 2
is given when there are at least two independently conducted
studies of level B or one trial of level A2, and a strength of conclusion
3 when there is one study of level B or level C. If no level of
conclusion could be calculated due to inconsistent literature, this
was indicated by level of conclusion ‘I’.
3. Results
3.1. Study selection
The search ended in September, 2015 and resulted in a total of
395 (Cochrane: 30, PubMed: 260, and WoS: 105) references and no
additional articles were obtained after searching in the references
of the included articles. After deduplication and the two screening
phases based on the selection criteria, 14 studies remained. Full
details on the selection process are represented in Fig. 1.
3.2. Study characteristics
The study population varied between 11 and 113 subjects. Nine
studies only investigated females (Kristjansson, 2004; Elliott et al.,
2006; Fernandez-de-las-Penas et al., 2008; Elliott et al., 2008a,
2008b, 2010; Rezasoltani et al., 2010; Rezasoltani et al., 2012; Elliott
et al., 2014), whereas five studies investigated both males and fe-
males (Hallgren et al., 1994; Elliott et al., 2011; Javanshir et al., 2011;
Ulbrich et al., 2012; Matsumoto et al., 2012). The CSA was assessed
in ten studies (Kristjansson, 2004; Fernandez-de-las-Penas et al.,
2008; Elliott et al., 2008b; Rezasoltani et al., 2010; Elliott et al.,
2010; Javanshir et al., 2011; Ulbrich et al., 2012; Rezasoltani et al.,
2012; Matsumoto et al., 2012; Elliott et al., 2014), while five studies
investigated the amount of fatty infiltration in the cervical muscles
(Hallgren et al., 1994; Elliott et al., 2006, 2008a, 2010, 2011). The
average age of each patient group varied between 26.9 and 42.0
years, and the average body mass index varied between 22.0 and
28.5 kg/m
2
.
3.3. Risk of bias within studies and level of evidence
Researchers agreed on 72 of 96 cases (75%). Differences were
discussed by both reviewers and consensus was met for all cases.
Scores ranged from 2 to a maximum of 7. Most methodological
deficits were caused by an unclear description of the control group.
Additionally, not all studies described a blind assessment for the
outcome measurement. Most studies scored well on describing the
exposure, and the patient population. A detailed description on the
risk of bias can be found in appendix 1.
3.4. Synthesis of results
3.4.1. Changes in CSA of neck muscles in neck pain patients
3.4.1.1. Flexor muscles. Four studies investigated the cervical flexor
muscles in chronic neck pain patients (Elliott et al., 2010; Javanshir
et al., 2011; Ulbrich et al., 2012; Elliott et al., 2014). In patients with
WADmoderate evidence existsfor an increased CSA of the superficial
flexor muscles (M. Sternocleidomastoideus) (level of conclusion 2)
(Elliott et al., 2010; Ulbrich et al., 2012; Elliott et al., 2014) and some
evidence for an increased CSA of the deep flexor muscles (M. Longus
Colli, and M. Longus Capitis)(level of conclusion 3) (Elliott et al., 2010,
2014). In chronic idiopathic neck pain patients some evidence exists
for an increased CSA of the superficial flexor muscles (level of evi-
dence 3) (Elliott et al., 2010, 2014), whereas some evidence exists for
a normal to decreased CSA of the deep flexor muscles (level of
conclusion3) (Elliott et al., 2010; Javanshir et al., 2011). These changes
of CSA in patients with WADwere highly influenced by the amount of
fatty infiltration (Elliott et al., 2014)(Table 2).
3.4.1.2. Extensor muscles. Six studies evaluated the morphology of
the extensor muscles (Fernandez-de-las-Penas et al., 2008; Elliott
et al., 2008b; Rezasoltani et al., 2010; Matsumoto et al., 2012;
Rezasoltani et al., 2012; Elliott et al., 2014). In chronic idio-
pathic neck pain patients some evidence exists for a decreased
CSA (level of conclusion 3) of the suboccipital muscles (M. Rectus
Capitis Maior, and M. Rectus Capitis minor) (Elliott et al., 2014)
and a normal to decreased CSA of the deep and superficial
Table 2 (continued )
Article Population Measurement technique Main results
Control (n) Patient (n)
Elliott et al. (2010)
a
31 females
(age: 27.0 ±5.47 yr;
BMI: 22.8 ±4.62 kg/m
2
)
78 females (age: 29.9 ±7.77 yr;
BMI: 25.2 ±5.74 kg/m
2
);
WAD II-patients with persisting
symptoms (3 monthse3 year)
MRI (1.5 LX GE &
Sonata 1.5T Magnet)
Longus colli,capitis,and SCM
WAD >control; WAD:
Deeper >superficial;
Elliott (2011) None 17 recovered (77.8% female;
age: 28.8 ±7.4 yr;
BMI: 25.1 ±4.5 kg/m
2
);
15 mild (68.8% female;
age: 36.7 ±9.7 yr;
BMI: 28.5 ±5.6 kg/m
2
);
12 moderate/severe (76.9% females;
age: 27.8 ±6.1 yr; BMI: 27.8 kg/m
2
);
WAD II epatients; Acute to 1-3-6 m
postinjury follow-up
MRI RCPmin,RCPMaj,multifidi;
semispinalis cervicus and capitis,
splenius capitis,and upper trapezius
baseline: recovered ¼mild
¼moderate; 3m, and 6m:
moderate >mild ¼recovered
(moderate: 3 m, and 6 m >baseline)
Hallgren et al. (1994) 5 (3 men, 2 women;
age: 38 yr)
6 women (age: 42.1 yr). INP patients MRI (Signa 1.5T) RCPMaj,RCPmin
INP >control
Yr, years; BMI, Body Mass Index; ¼, equal; >, more than; <, less than; SCM, M. Sternocleidomastoideus; RCPMaj, M. Rectus Capitis Posterior Maior; RCPmin, M. Rectus Capitis
posterior minor.
The data of the study of Ulbrich et al. (2011) (Ulbrich et al., 2011) was included in their study of 2012 (Ulbrich et al., 2012), and therefore not mentioned separately.
a
Results from the same study of Elliott et al. (2010).
b
Only significant values are given.
R. De Pauw et al. / Manual Therapy xxx (2015) 1e84
Please cite this article in press as: De Pauw R, et al., Does muscle morphology change in chronic neck pain patients? eA systematic review,
Manual Therapy (2015), http://dx.doi.org/10.1016/j.math.2015.11.006

extensor muscles (level of conclusion 3) (Fernandez-de-las-Penas
et al., 2008; Elliott et al., 2014). In patients with WAD some ev-
idence is available for a normal CSA of the sub-occipital muscles
(level of conclusion 3) (Elliott et al., 2008b, 2014) and a normal to
increased CSA of the superficial extensor muscles at higher cer-
vical levels, such as the M. Trapezius, M. Splenius Capitis, and M.
Splenius Cervicus (level of conclusion 3) (Elliott et al., 2008b;
Matsumoto et al., 2012; Elliott et al., 2014). In contrast, some
evidence exists for a normal to decreased CSA at lower cervical
levels (level of conclusion 3) (Elliott et al., 2008b; Matsumoto
et al., 2012; Elliott et al., 2014). One author additionally
described the CSA of the total extensor group, and found no
increased CSA (Ulbrich et al., 2012). As much inconsistency exists
between different research papers for the CSA of the M. Multi-
fidus, for which most authors reported an increased CSA
(Matsumoto et al., 2012; Elliott et al., 2014), one ultrasonography-
based study found a decreased CSA (Kristjansson, 2004), and one
found no differences in CSA at the upper cervical levels (Elliott
et al., 2014), no level of conclusion was assigned (level of
conclusion I). In both chronic idiopathic neck pain patients and
patients with WAD a decreased CSA was reported in the sub-
occipital muscles after adjusting for the amount of fatty infiltra-
tion (Elliott et al., 2014)(Table 2).
To summarise changes in CSA of neck muscles in neck pain
patients, moderate evidence is available for morphological changes
in the cervical flexors of chronic neck pain patients. These changes
consist of a higher CSA of all flexor muscles, except for the deeper
flexor muscles of chronic idiopathic neck pain patients. Regarding
the extensor muscles, an increased CSA for all muscles at higher
cervical levels was seen in patients with WAD. This increase was
however reversed for the sub-occipital muscles after adjusting the
CSA for the amount of fat. In patients with chronic idiopathic neck
pain most studies reported a decreased CSA of almost all extensor
muscles.
3.4.2. Fatty infiltration in the neck muscles of chronic neck pain
patients
Five studies investigated the amount of fatty infiltration in the
cervical flexors and/or extensors (Hallgren et al., 1994; Elliott et al.,
2006, 2008a, 2010, 2011). Two studies investigated fatty infiltra-
tion in chronic idiopathic neck pain patients (Hallgren et al., 1994;
Elliott et al., 2008a), whereas two other studies evaluated this in
patients with WAD (Elliott et al., 2006, 2011). A higher amount of
fatty infiltration was found in muscles of patients with WAD
(Elliott et al., 2008a). This increase was reported in the cervical
extensor muscles with a clear cephalocaudate decline that was
found in all extensor muscles, except for the M. Multifidus (Elliott
et al., 2006). However, this increased fatty infiltration was only
found in patients who developed long term moderate to severe
symptoms (Elliott et al., 2011). Another study also reported this
increase in the cervical flexor muscles with a higher fat amount in
the deep flexor muscles compared to the superficial flexor muscles
(Elliott et al., 2010). In chronic idiopathic neck pain patients, in-
dications for an increased amount of fatty infiltration in the sub-
occipital muscles was found (Hallgren et al., 1994). However,
recent research has only found an increased fatty infiltration in
patients with WAD, and not in chronic idiopathic neck pain pa-
tients (Elliott et al., 2008a). In conclusion, there is some evidence
for an increased amount of fat in both flexors and extensors of the
cervical spine (level of conclusion 3) (Table 2).
4. Discussion
The goal of the present systematic review was to evaluate
morphological changes in chronic neck pain patients in both
Fig. 1. Selection process.
R. De Pauw et al. / Manual Therapy xxx (2015) 1e85
Please cite this article in press as: De Pauw R, et al., Does muscle morphology change in chronic neck pain patients? eA systematic review,
Manual Therapy (2015), http://dx.doi.org/10.1016/j.math.2015.11.006

patients with chronic idiopathic neck pain and patients with WAD.
Furthermore, we looked at the existence of potential differences
between these groups of patients with neck pain.
4.1. Cross-sectional area
In patients with WAD a tendency for an increased CSA of the
cervical flexors has been found, while evidence for changes of the
extensor muscles remains inconclusive. Preliminary evidence exists
for an increased CSA of the superficial extensor muscles at higher
cervical levels concomitantly with a normal to decreased CSA of the
lower superficial extensor muscles. The sub-occipital muscles only
have a decreased CSA after adjustment for the amount of fatty
infiltration. Important to notice are the conflicting results regarding
the CSA of the M. Multifidus in patients with WAD: MRI-based
studies have reported an increased, whereas an ultrasound-based
study has demonstrated a decreased CSA (Kristjansson, 2004).
Differences may be assigned to potential differences in both tech-
niques. MRI is up until now still seen as golden standard for
measuring muscle size in vivo (Mitsiopoulos et al., 1998). Although
ultrasound-based studies have also been tested on validity in the
neck musculature, studies were mostly performed on healthy
subjects (Javanshir et al., 2010). Furthermore, making a distinction
between fat and muscle tissue is more delicate on ultrasound im-
ages due to image-similarities, which is in contrast with MRI, where
both tissues are easily distinguished (Hides et al., 1992; Javanshir
et al., 2010; Westbrook and Roth, 2011). Performing a comparison
between studies using ultrasonography and studies using MRI may
be thus affected by differences in detection of varying tissues
(Javanshir et al., 2010).
Many authors have proposed mechanisms for the increased
CSA seen in patients with WAD. A first mechanism involves a
constant muscle contraction, which ensures the limitation of
greater neck movement and as a consequence may prevent from
neck pain (Ulbrich et al., 2011). The appearance of fatty infiltration
has also been proposed as an explanatory mechanism for the
increased CSA. This mechanism is furthermore endorsed by the
reversibility of the CSA in neck muscles of patients with WAD after
factoring for fatty infiltration (Elliott et al., 2014). A higher fat
content could alter and expand the myofascial border, leading to
the appearance of pseudohypertrophy (Lovitt et al., 2006; Elliott
et al., 2008b).
The higher CSA was most prominent at the uppermost cer-
vical segments, while a lower CSA was found at the lower seg-
ments. This phenomenon could be clarified by two potential
mechanisms: the appearance of pseudohypertrophy or a higher
muscle activity of the upper cervical segments. A first hypothesis
is that segments could be more prone to pseudohypertrophy
since a clear cephalocaudate decline of fatty infiltration has been
reported in the cervical extensor muscles (Elliott et al., 2006).
Secondly, a relatively higher muscle activity at the upper cervical
segments compared to lower muscle activity at lower cervical
levels may also explain this cephalocaudate decline in CSA.
Muscle functional MRI studies have already demonstrated a
heightened activity of the cervical muscles at these higher levels
and a reduced activity at lower levels in patients with neck pain
compared to healthy controls (Cagnie et al., 2011; O'Leary et al.,
2011). The increased CSA does furthermore not occur immedi-
ately after the traumatic event, but occurs after a certain time
interval (Ulbrich et al., 2011). These changes do furthermore not
occur in all patients with WAD (Ulbrich et al., 2012), but exclu-
sively in those who suffer from moderate to severe disability
(Elliott et al., 2011).
In patients with idiopathic neck pain no increase in CSA has
been found. In fact, muscle atrophy seems to be the only
mechanism appearing in this patient group. Patients with neck pain
might exhibit avoidance behaviour and pain-related fear, which is
part of a maladaptive process (Landers et al., 2008). This could
contribute to muscle disuse, which may reflect a protective strategy
that is in accordance to the pain adaptation model (Lund et al.,
1991). Atrophy was however not found in all muscles indicating
that the observed atrophy is potentially not only just part of general
disuse atrophy or psychological factors. Reflex inhibition and
changes in recruitment patterns may also account for this selective
muscle degeneration in chronic neck pain. According to the theory
of Hodges and Tucker (2011), redistribution of activity within and
between muscles may take place as a maladaptive strategy to adapt
to pain (Hodges and Tucker, 2011). This may explain why an
increased activity (Falla, 2004) and CSA was found in the sterno-
cleidomastoid muscle.
4.2. Fatty infiltration
Besides changes in CSA, some evidence is available for the
occurrence of fatty infiltration, which is an indication of muscle
degeneration, in both cervical flexor and extensor muscles. This
infiltration does however only occur in muscles of patients with
WAD ( Elliott et al., 2014), and mainly in those patients who suffer
from moderate to severe complaints. However, only one study
investigated the appearance of fatty infiltration in both patients
with WAD and idiopathic neck pain. This may suggest that the
traumatic-induced character of this neck pain type could be
responsible for the occurrence of fatty infiltration. Similarly, this
feature also appears in other musculoskeletal injury-related
disorders, such as rotator cuff repair (Meyer et al., 2004;
Gerber et al., 2007). This corresponds with the results in this
study, as fatty infiltration seems to only occur in trauma-induced
neck pain and not in idiopathic neck pain, which is not mediated
by a traumatic event. The amount of fatty infiltration seems to
occur in a cephalocaudate decline, indicating muscles at higher
cervical levels may be more prone to the appearance of this
infiltration. The underlying mechanisms for the appearance of
fatty infiltration are however still unclear, and different causal
mechanisms have been proposed (Elliott, 2011). Disuse may be a
first mechanism responsible for the occurrence of fatty infiltra-
tion complementary to a decreased CSA (Hides et al., 1994).
Secondly, central mechanisms, such as chronic denervation
(Andary et al., 19 98; Dulor et al., 1998), motoneuron lesions (Ryan
et al., 2002), and minor injuries to the spinal cord (Gorgey and
Dudley, 2006; Elliott et al., 2012) and/or higher brain centres
(Ryan et al., 2002) have also been associated with fatty infiltra-
tion and are known to alter pain perception (Bolay and
Moskowitz, 20 02). These alterations have furthermore been re-
ported in patients with WAD (Van Oosterwijck et al., 2013).
Nevertheless, evidence is currently lacking for the occurrence of
injuries to the central nervous system in patients with WAD
(V
allez García et al., 2014). In addition, fatty infiltration has been
found to be weakly associated with post-traumatic stress (Elliott
et al., 2009, 2011), which commonly occurs in patients with WAD
(Sullivan et al., 2009). The presence of elevated inflammatory
biomarkers has also been postulated as a possible mechanism for
muscle degeneration, although recent findings could not fully
confirm this hypothesis (Sterling et al., 2013).
Our results indicate that different mechanisms might be
responsible for the occurrence of fatty infiltration in the deep
compared to the superficial neck flexor muscles. This difference
may be related to the reported functional changes between these
muscles, which is reflected in an increased activity of the su-
perficial muscles and a decreased activity of the deeper cervical
muscles (Falla, 2004). Alternatively, the deeper muscles may be
R. De Pauw et al. / Manual Therapy xxx (2015) 1e86
Please cite this article in press as: De Pauw R, et al., Does muscle morphology change in chronic neck pain patients? eA systematic review,
Manual Therapy (2015), http://dx.doi.org/10.1016/j.math.2015.11.006

more prone to central mechanisms since these muscles do
possess a larger density of muscle spindles (Boyd-Clark et al.,
2002).
4.3. Muscle fibre typing
To the best of our knowledge, no studies have analyzed differ-
ences in fibre-typing, in patients with chronic idiopathic neck pain
or patients with WAD. Only one study-group has reported an
ongoing transition from the “oxidative”type I fibres to the “glyco-
lytic”type II fibres in post-surgery patients (Weber et al., 1993;
Uhlig et al., 1995).
4.4. Limitations and suggestion for further research
It is important to highlight some methodological limitations
of the current systematic review. Firstly, a meta-analysis was not
considered due to the low amount of studies that were found and
the variability in the used measurement techniques, outcome
measures and muscles investigated. Many of the included studies
were carried out by the same research group, which could be
considered as a limitation of this systematic review. To enhance
methodological quality, future studies should consider
mentioning a clear description of their control group, blinding
their analysis, and include important confounding factors like
age, BMI, and gender, as these factors may potentially influence
the CSA and the amount of fatty infiltration. Although ultraso-
nography and MRI are both valid methods for analysing CSA
(Hides et al., 1995; Dupont et al., 2001; Khoury et al., 2008),
comparing one to another should be done with precautions. As
proposed by Elliott et al. (2014) further research could focus on
3D-volume muscle changes (Elliott et al., 2014) and/or Diffusion
Tensor Imaging (DTI) (Elliott et al., 2012), since these techniques
might give us more details behind these morphological changes.
It might also be interesting to include a reference scan of other
muscles such as the calf-muscles or M. Quadriceps to exclude a
generic change in muscle morphology. Only one article has re-
ported the CSA of different muscles adjusted for the amount of
fatty infiltration. Since some evidence exists for the appearance
of fatty infiltration, certainly in patient with WAD, it seems
mandatory that future research tries to accommodate for this
problem, which would make comparison between different
studies easier.
5. Conclusion
Evidence exists for morphological changes in neck muscles of
chronic neck pain patients. The results of this study indicate a
differentiation in muscle morphology between chronic idiopathic
neck pain patients and patients with WAD. In chronic idiopathic
neck pain, a decreased CSA was found in most muscles, which may
reflect gene ral disuse. In pat ients with WAD, an inc reased CSA was
found in the deep cervical muscles and in muscles at higher cer-
vical levels, which may probably be related to an increased
amount of fatty infiltration. The factors responsible for the
occurrence of these changes and their association with clinical
symptoms are not clear. Further research on the association be-
tween the presence of fatty infiltration, changes in CSA, and
clinical symptoms seems therefore mandatory. Furthermore,
cross-sectional studies should include a clear description of the
control group and blind their assessment, while cohort studies
should try to give more details on follow-up and correct for
possible confounders. Morphological changes may furthermore
have an important impact on the daily life of the patient, and
should be considered when treating neck pain patients.
Appendix 1
Risk of bias of CaseeControl studies
Patient group Control group Selection bias Exposure Blinded Confounders Score
Fernandez-de-las-Penas et al. (2008) 1 0 0 1 1 0 3/6
Rezasoltani et al. (2012) 1 0 1 1 0 0 3/6
Rezasoltani et al. (2010) 1 0 1 1 0 0 3/6
Javanshir et al. (2011) 1 0 0 1 1 0 3/6
Hallgren et al. (1994) 0 1 0 1 0 0 2/6
Elliott et al. (2006) 1 0 1 1 0 1 4/6
Elliott et al. (2008a) 1 1 1 1 0 1 5/6
Elliott et al. (2008b) 1 0 1 1 0 1 4/6
Elliott et al. (2010) 1 0 1 1 0 1 4/6
Elliott et al. (2014) 1 0 1 1 0 1 4/6
Kristjansson (2004) 1 1 1 1 0 1 5/6
Patient group, was the patient group adequately defined (eg. Pain free days, level of pain, pain region)?; Control group, was the control group adequately defined?; Selection
bias, Was selection bias adequately excluded (eg. Recruitment in the same population, clearly described in- and exclusion criteria)?; Exposure, Was there a clear description
of the exposure in the study; Blinded, was the assessor of the study blinded for the patient's condition?; Confounders, Were confounders adequately addressed (eg. Age,
Sex and BMI).
Risk of bias of Cohort studies
Population Selection bias Exposure Outcome Blinded Follow up Loss to follow up Confounders Score
Ulbrich et al. (2012) 1 1 1 1 1 1 0 1 7/8
Matsumoto et al. (2012) 0 1 1 1 0 1 0 1 5/8
Elliott (2011) 1 1 1 1 0 1 1 0 6/8
Population, was the patient/control group adequately defined (eg. Pain free days, level of pain, pain region)?; Selection bias, Was selection bias adequately excluded (eg.
Recruitment in the same population, clearly described in- and exclusion criteria)?; Exposure, Was there a clear description of the exposure in the study; Outcome, Was the
outcome clearly described?; Blinded, was the assessor of the study blinded for the patient's condition?; Follow-up, Was the follow-up period sufficient to measure an effect?;
Loss to follow-up, Were drop-out cases clearly described? Confounders, Were confounders adequately addressed (eg. Age, Sex and BMI)?
R. De Pauw et al. / Manual Therapy xxx (2015) 1e87
Please cite this article in press as: De Pauw R, et al., Does muscle morphology change in chronic neck pain patients? eA systematic review,
Manual Therapy (2015), http://dx.doi.org/10.1016/j.math.2015.11.006

References
Andary MT, Hallgren RC, Greenman PE, Rechtien JJ. Neurogenic atrophy of sub-
occipital muscles after a cervical injury. Am J Phys Med Rehabil 1998;77(6):
545e9.
Bolay H, Moskowitz MA. Mechanisms of pain modulation in chronic syndromes.
Neurology 2002;59(5 Suppl. 2):S2e7.
Boyd-Clark L, Briggs C, Galea M. Muscle spindle distribution, morphology, and
density in longus colli and multifidus muscles of the cervical spine. Spine
2002;27(7):694e701.
Cagnie B, O'Leary S, Elliott J, Peeters I, Parlevliet T, Danneels L. Pain-induced changes
in the activity of the cervical extensor muscles evaluated by muscle functional
magnetic resonance imaging. Clin J Pain 2011;27(5):392e7. http://dx.doi.org/
10.1097/AJP.0b013e31820e11a2.
Dulor J-P, Cambon B, Vigneron P, Reyne Y, Nougu
es J, Casteilla L, et al. Expression of
specific white adipose tissue genes in denervation-induced skeletal muscle
fatty degeneration. FEBS Lett 1998;439(1):89e92.
Dupont AC, Sauerbrei EE, Fenton PV, Shragge PC, Loeb GE, Richmond FJR. Real-time
sonography to estimate muscle thickness: comparison with MRI and CT. J Clin
Ultrasound 2001;29(4):230e6.
Elliott JM. Are there implications for morphological changes in neck muscles after
whiplash injury? Spine 2011;36(25 Suppl):S205e10. http://dx.doi.org/10.1097/
BRS.0b013e3182387f57.
Elliott J, Jull G, Noteboom JT, Darnell R, GallowayG, Gibbon WW. Fatty infiltration in
the cervical extensor muscles in persistent whiplash-associated disorders: a
magnetic resonance imaging analysis. Spine 2006;31(22):E847e55. http://
dx.doi.org/10.1097/01.brs.0000240841.07050.34.
Elliott J, Sterling M, Noteboom JT, Darnell R, Galloway G, Jull G. Fatty infiltrate in the
cervical extensor muscles is not a feature of chronic, insidious-onset neck pain.
Clin Radiol 2008a;63(6):681e7. http://dx.doi.org/10.1016/j.crad.2007.11.011.
Elliott J, Jull G, Noteboom JT, Galloway G. MRI study of the cross-sectional area for
the cervical extensor musculature in patients with persistent whiplash asso-
ciated disorders (WAD). Man Ther 2008b;13(3):258e65. http://dx.doi.org/
10.1016/j.math.2007.01.012.
Elliott J, Sterling M, Noteboom JT, Treleaven J, Galloway G, Jull G. The clinical pre-
sentation of chronic whiplash and the relationship to findings of MRI fatty
infiltrates in the cervical extensor musculature: a preliminary investigation. Eur
Spine J Offic Publ Eur Spine Soc Eur Spinal Deformity Soc Eur Sect Cerv Spine
Res Soc 2009;18(9):1371e8. http://dx.doi.org/10.1007/s00586-009-1130-6.
Elliott JM, O'Leary S, Sterling M, Hendrikz J, Pedler A, Jull G. Magnetic resonance
imaging findings of fatty infiltrate in the cervical flexors in chronic whiplash.
Spine 2010;35(9):948e54. http://dx.doi.org/10.1097/BRS.0b013e3181bb0e55.
Elliott J, Pedler A, Kenardy J, Galloway G, Jull G, Sterling M. The temporal devel-
opment of fatty infiltrates in the neck muscles following whiplash injury: an
association with pain and posttraumatic stress. PloS One 2011;6(6):e21194.
http://dx.doi.org/10.1371/journal.pone.0021194.
Elliott JM, Pedler AR, Cowin G, Sterling M, McMahon K. Spinal cord metabolism and
muscle water diffusion in whiplash. Spinal Cord 2012;50(6):474e6. http://
dx.doi.org/10.1038/sc.2011.17.
Elliott JM, Pedler AR, Jull GA, Van Wyk L, Galloway GG, O'Leary SP. Differential
changes in muscle composition exist in traumatic and nontraumatic neck pain.
Spine 2014;39(1):39e47.
Falla D. Unravelling the complexity of muscle impairment in chronic neck pain. Man
Ther 2004;9(3):125e33.
Falla D, Jull G, Edwards S, Koh K, Rainoldi A. Neuromuscular efficiency of the
sternocleidomastoid and anterior scalene muscles in patients with chronic neck
pain. Disabil Rehabil 2004;26(12):712e7. http://dx.doi.org/10.1080/
09638280410001704287.
Fejer R, Kyvik KO, Hartvigsen J. The prevalence of neck pain in the world popula-
tion: a systematic critical review of the literature. Eur Spine J 2006;15(6):
834e48.
Fernandez-de-las-Penas C, Albert-Sanchis JC, Buil M, Benitez JC, Alburquerque-
Sendin F. Cross-sectional area of cervical multifidus muscle in females with
chronic bilateral neck pain compared to controls. J Orthop Sports Phys Ther
2008;38(4):175e80. http://dx.doi.org/10.2519/jospt.2008.2598.
Gerber C, Schneeberger AG, Hoppeler H, Meyer DC. Correlation of atrophy and fatty
infiltration on strength and integrity of rotator cuff repairs: a study in thirteen
patients. J Shoulder Elb Surg 2007;16(6):691e6.
Gorgey A, Dudley G. Skeletal muscle atrophy and increased intramuscular fat after
incomplete spinal cord injury. Spinal Cord 2006;45(4):304e9.
Hallgren RC, Greenman PE, Rechtien JJ. Atrophy of suboccipital muscles in patients
with chronic pain: a pilot study. J Am Osteopath Assoc 1994;94(12):1032e8.
Hides JA, Cooper DH, Stokes MJ. Diagnostic ultrasound imaging for measurement of
the lumbar multifidus muscle in normal young adults. Physiother Theory Pract
1992;8(1):19e26.
Hides JA, Stokes MJ, Saide M, Jull GA, Cooper DH. Evidence of lumbar multifidus
muscle wasting ipsilateral to symptoms in patients with acute/subacute low
back pain. Spine 1994;19(2):165e72.
Hides JA, Richardson CA, Jull GA. Magnetic resonance imaging and ultrasonography
of the lumbar multifidus muscle: comparison of two different modalities. Spine
1995;20(1):54e8.
Hodges PW, Tucker K. Moving differently in pain: a new theory to explain the
adaptation to pain. Pain 2011;152(3 Suppl):S90e8.
Hoy D, Protani M, De R, Buchbinder R. The epidemiology of neck pain. Best Pract Res
Clin Rheumatol 2010;24(6):783e92.
Javanshir K, Amiri M, Mohseni-Bandpei MA, Rezasoltani A, Fern
andez-de-las-
Pe~
nas C. Ultrasonography of the cervical muscles: a critical review of the
literature. J Manip Physiol Ther 2010;33(8):630e7.
Javanshir K, Rezasoltani A, Mohseni-Bandpei MA, Amiri M, Ortega-Santiago R, Fer-
nandez-de-Las-Penas C. Ultrasoundassessment of bilaterallongus colli muscles in
subjects with chronic bilateral neck pain. Am J Phys Med Rehabil/Assoc Acad
Physiatr 2011;90(4):293e301. http://dx.doi.org/10.1097/PHM.0b013e31820173e5.
Khoury V, Cardinal 
E, Brassard P. Atrophy and fatty infiltration of the supraspinatus
muscle: sonography versus MRI. Am J Roentgenol 2008;190(4):1105e11.
Kristjansson E. Reliability of ultrasonography for the cervical multifidus muscle in
asymptomatic and symptomatic subjects. Man Ther 20 04;9(2):83e8. http://
dx.doi.org/10.1016/s1356-689x(03)00059-6.
Landers MR, Creger RV, Baker CV, StutelbergKS. The use of fear-avoidance beliefs and
nonorganic signs in predicting prolonged disability in patients with neck pain.
Man Ther 2008;13(3):239e48. http://dx.doi.org/10.1016/j.math.2007.01.010.
Lovitt S, Moore SL, Marden FA. The use of MRI in the evaluation of myopathy. Clin
Neurophysiol 2006;117(3):486e95.
Lund JP, Donga R, Widmer CG, Stohler CS. The pain-adaptation model: a discussion
of the relationship between chronic musculoskeletal pain and motor activity.
Can J Physiol Pharmacol 1991;69(5):683e94.
Matsumoto M, Ichihara D, Okada E, Chiba K, Toyama Y, Fujiwara H, et al. Cross-
sectional area of the posterior extensor muscles of the cervical spine in whip-
lash injury patients versus healthy volunteerse10 year follow-up MR study.
Injury 2012;43(6):912e6. http://dx.doi.org/10.1016/j.injury.2012.01.017.
Meyer DC, Hoppeler H, von Rechenberg B, Gerber C. A pathomechanical concept
explains muscle loss and fatty muscular changes following surgical tendon
release. J Orthop Res 2004;22(5):1004e7.
Mitsiopoulos N, Baumgartner RN, Heymsfield SB, Lyons W, Gallagher D, Ross R.
Cadaver validation of skeletal muscle measurement by magnetic resonance
imaging and computerized tomography. J Appl Physiol 1998;85(1):115e22.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic
reviews and meta-analyses: the PRISMA statement. Ann Intern Med
2009;151(4):264e9.
O'Leary S, Cagnie B, Reeve A, Jull G, Elliott JM. Is there altered activity of the
extensor muscles in chronic mechanical neck pain? A functional magnetic
resonance imaging study. Arch Phys Med Rehabilitation 2011;92(6):929e34.
Rezasoltani A, Ali-Reza A, Khosro KK, Abbass R. Preliminary study of neck muscle
size and strength measurements in females with chronic non-specific neck pain
and healthy control subjects. Man Ther 2010;15(4):400e3. http://dx.doi.org/
10.1016/j.math.2010.02.010.
Rezasoltani A, Ahmadipoor A, Khademi-Kalantari K, Javanshir K. The sign of uni-
lateral neck semispinalis capitis muscle atrophy in patients with chronic non-
specific neck pain. J Back Musculoskelet Rehabilitation 2012;25(1):67e72.
http://dx.doi.org/10.3233/bmr-2012-0303.
Ryan AS, Dobrovolny CL, Smith GV, Silver KH, Macko RF. Hemiparetic muscle
atrophy and increased intramuscular fat in stroke patients. Arch Phys Med
Rehabilitation 2002;83(12):1703e7.
Spitzer WO, Skovron ML, Salmi LR, Cassidy JD, Duranceau J, Suissa S, et al. Scientific
monograph of the Quebec Task Force on Whiplash-Associated Disorders:
redefining “whiplash”and its management. Spine 1995;20(8 Suppl):1Se73S.
Sterling M, McLean SA, Sullivan MJL, Elliott JM, Buitenhuis J, Kamper SJ. Potential
processes involved in the initiation and maintenance of whiplash-associated
disorders: discussion paper 3. Spine (Phila Pa 1976) 2011;36:S322e9.
Sterling M, Elliott JM, Cabot PJ. The course of serum inflammatory biomarkers
following whiplash injury and their relationship to sensory and muscle
measures: a longitudinal cohort study. PloS One 2013;8(10).
Sullivan MJ, Thibault P,Simmonds MJ, Milioto M, Cantin A-P,Velly AM. Pain, perceived
injustice and the persistence of post-traumatic stress symptoms during the
course of rehabilitation for whiplash injuries. Pain 2009;145(3):325e31.
Uhlig Y, Weber BR, Grob D, Muntener M. Fiber composition and fiber trans-
formations in neck muscles of patients with dysfunction of the cervical spine.
J Orthop Res official Publ Orthop Res Soc 1995;13(2):240e9. http://dx.doi.org/
10.1002/jor.1100130212.
Ulbrich EJ, Anderson SE, Busato A, Abderhalden S, Boesch C, Zimmermann H, et al.
Cervical muscle area measurements in acute whiplash patients and controls.
J Magn Reson Imaging JMRI 2011;33(3):668e75. http://dx.doi.org/10.1002/
jmri.22446.
Ulbrich EJ, Aeberhard R, Wetli S, Busato A, Boesch C, Zimmermann H, et al. Cervical
muscle area measurements in whiplash patients: acute, 3, and 6 months of
follow-up. J Magn Reson Imaging JMRI 2012;36(6):1413e20. http://dx.doi.org/
10.1002/jmri.23769.
V
allez García D, Dierckx RA, Otte A, Holstege G. Whiplash, real or not real? A review
and new concept. PET SPECT Neurol 2014:947e63.
Van Oosterwijck J, Nijs J, Meeus M, Paul L. Evidence for central sensitization in
chronic whiplash: a systematic literature review. Eur J Pain 2013;17(3):
299e312.
Weber BR, Uhlig Y, Grob D, Dvorak J, Muntener M. Duration of pain and muscular ad-
aptationsin patients with dysfunction of the cervical spine.J Orthop Res OfficPubl
Orthop Res Soc 1993;11(6):805e10. http://dx.doi.org/10.1002/jor.1100110605.
Westbrook C, Roth CK. MRI in Practice. John Wiley &Sons; 2011. p. 29.
R. De Pauw et al. / Manual Therapy xxx (2015) 1e88
Please cite this article in press as: De Pauw R, et al., Does muscle morphology change in chronic neck pain patients? eA systematic review,
Manual Therapy (2015), http://dx.doi.org/10.1016/j.math.2015.11.006