10 1002@ejp 1632

Spinal manipulation for the management of cervicogenic headache: a systematic review and
meta-analysis
Matthew Fernandez 1,3, Craig Moore 2,3, Jinghan Tan1, Derrick Lian 1, Jeremy Nguyen 1, Andrew
Accepted Article
Bacon 1, Brie Christie 1, Isabella Shen 1, Thomas Waldie 1, Danielle Simonet 1, André Bussières 4,5.
1. Macquarie University, Sydney, Australia
2. University of Technology, Sydney, Australia
3. Chiropractic Academy for Research Leadership (CARL), Sydney, Australia
4. McGill University, Montreal, Québec, Canada
5. Université du Québec à Trois-Rivières, Trois-Rivières, Québec, Canada
Corresponding author email: matthew.fernandez@mq.edu.au

Corresponding author phone: 02 9850 9523
Funding sources: No funding sources supported this work.
Conflict of interest: None declared.
Abstract
Background: Spinal manipulative therapy (SMT) is frequently used to manage cervicogenic
headache (CGHA). No meta-analysis has investigated the effectiveness of SMT exclusively for
CGHA.
Objective: Evaluate the effectiveness of SMT for CGHA.
Databases and Data Treatment: Five databases identified randomized controlled trials
comparing SMT with other manual therapies. The PEDro scale assessed the risk-of-bias. Pain and
disability data were extracted and converted to a common scale. A random effects model was
used for several follow-up periods. GRADE described the quality of evidence.
Results: Seven trials were eligible. At short-term follow-up, there was a significant, small effect
favouring SMT for pain intensity (mean difference [MD] -10.88 [95% CI, -17.94, -3.82]) and small
effects for pain frequency (standardized mean difference [SMD] -0.35 [95%CI, -0.66, -0.04]).
There was no effect for pain duration (SMD -0.08 [95%CI, -0.47, 0.32]). There was a significant,
small effect favoring SMT for disability (MD -13.31 [95% CI, -18.07, -8.56]). At intermediate
follow-up, there was no significant effects for pain intensity (MD -9.77 [-24.21 to 4.68]) and a
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significant, small effect favoring SMT for pain frequency (SMD -0.32 [-0.63 to -0.00]). At long-
term follow-up, there was no significant effects for pain intensity (MD -0.76 [-5.89 to 4.37]) and
for pain frequency (SMD -0.37 [-0.84 to 0.10]).
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Conclusion: For CGHA, SMT provides small, superior short-term benefits for pain intensity,
frequency and disability but not pain duration, however, high-quality evidence in this field is
lacking. The long-term impact is not significant.
Significance: CGHA are a common headache disorder. SMT can be considered an effective
treatment modality, with this review suggesting it providing superior, small, short-term effects
for pain intensity, frequency and disability when compared to other manual therapies. These
findings may help clinicians in practice better understand the treatment effects of SMT alone for
CGHA.
Key words: cervicogenic, headache, spinal manipulation, manual therapy, systematic review,
meta-analysis

Accepted Article
What’s already known about this topic?
 Previous systematic reviews have shown that SMT might be a beneficial modality for
reducing pain and disability associated with CGHA.
What does this study add?

 This meta-analysis reports the estimate of the size of the effects for SMT compared to
other manual therapies for CGHA.
 These findings may help clinicians to better understand the treatment effects of SMT
alone for CGHA.
 Such findings may assist with the shared decision-making process regarding treatment
options for this common headache disorder.

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Introduction
Cervicogenic headache (CGHA) is believed to arise as a secondary disorder from pain in the
cervical spine (Zito et al., 2006). The prevalence of CGHA is estimated to effect up to 4.1% of the
general population (O. Sjaastad & Bakketeig, 2008) and makes up approximately 15%-20% of all
patients who complain of headaches (Haldeman & Dagenais, 2001). Limited evidence also
suggests CGHA impact on quality of life is substantial and comparable to migraine and episodic
tension-type headache (Suijlekom et al., 2003). CGHA is characterised by pain that begins in the
neck or occipital region and can move to several regions of the face and head (Bogduk, 1992;
Bogduk & Govind, 2009). The anatomical basis for this observation likely relates to convergence
of both the upper cervical segments and trigeminal nociceptive afferents within the trigemino-
cervical complex (Bogduk, 2014). The Cervicogenic Headache International Study Group (CHISG)
classifies CGHA as side-locked head pain worsened by neck movement or sustained improper
positioning, restricted cervical range of motion, and ipsilateral shoulder and arm pain (O.
Sjaastad et al., 1998). Despite this relatively strict criterion, it can be difficult to clinically
diagnose CGHA. For instance, sharp pain in the occipital region may reflect occipital neuralgia,
which can mimic a CGHA (Barmherzig & Kingston, 2019), while overlapping signs and symptoms
with other forms of headaches can imitate CGHA, including neck pain, nausea, vomiting,
photophobia and phonophobia associated with migraine headaches (Fredriksen et al., 2015a; O
Sjaastad, 2008).

People with CGHA regularly consult providers of manual therapy as part of their headache
management (Moore et al., 2017). With a lack of effective drug treatments for CGHA, various
treatment modalities have been proposed, including spinal mobilisation, massage and
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endurance-based cervico-scapular exercises (Jull et al., 2002). Spinal manipulative therapy (SMT),
as commonly performed by chiropractors, is another popular approach (Wells et al., 2011). SMT
is defined as a manually applied, high velocity and low amplitude force, directed at specific spinal
segments to create joint movement at or beyond the normal joint end-range (Gross et al., 2010).
A number of contemporary systematic reviews have shown that SMT might be a beneficial
modality for reducing pain associated with CGHA (Chaibi & Russell, 2012; Coelho et al., 2019;
Garcia et al., 2016; Racicki et al., 2013). These systematic reviews based their conclusions on
multimodal treatment studies that incorporated or combined massage, spinal mobilisation and
exercise, with and without SMT (Chaibi & Russell, 2012; Coelho et al., 2019; Garcia et al., 2016;
Racicki et al., 2013).
In spite of this, the most recent evidence-based clinical practice guidelines for the management
of headaches associated with neck pain, suggests that there was no added benefit from
combining spinal manipulation, spinal mobilisation and exercise than providing either of these
interventions in isolation for CGHA (Côté et al., 2019). Given that previous systematic reviews
did not specifically compare SMT in isolation to other manual therapies in the form of a meta-
analysis, it is currently not known whether SMT is superior to other manual therapy
interventions for CGHA. Thus, the objective of this review was to summarize, critically appraise,
analyse and interpret the available evidence comparing SMT to other manual therapies for the
management of CGHA.
Methods
A priori protocol for this systematic review and meta-analysis was registered with PROSPERO
(CRD42019141633).
Literature Search

The PRISMA Statement was used to guide the conduct and reporting of the study (Liberati et al.,
2009). This study originally searched the following electronic databases from inception to May
2019, Medline, Mantis, PEDro and Cochrane Central Register of Controlled Trials. MeSH terms
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related to cervicogenic; headache; spinal manipulation; manual therapy; and randomised
controlled trial were used. Four reviewers evaluated the titles and abstracts (DL, JN, ABa, BC).
The literature search was limited to English only studies, with reference lists of relevant reviews,
trials and clinical guidelines screened for additional studies. An updated search was conducted by
one reviewer (MF), which included Embase as well as the above-mentioned databases from
inception to December 2019. In the updated screening for potential eligible studies, one
reviewer (MF) assessed whether the study fulfilled the inclusion criteria. Two additional
reviewers (CM, AB) were consulted in cases of disagreement. The updated search strategy
utilised in this review is outlined in Appendix 1.
Study Selection
Eligible trials needed to enrol patients who experience and report CGHA and;
1. Adults with CGHA diagnosed by a certified medical or allied health practitioner, using the
International Headache Society (IHS) ("The International Classification of Headache Disorders,
3rd edition (beta version)," 2013) or CHISG (O. Sjaastad et al., 1998);
2. The primary treatment was SMT;
3. The comparison group received other forms of manual therapy including: spinal mobilisation
(i.e., a low-grade/velocity, small or large amplitude passive, repetitive, rhythmic oscillatory
movement, applied with either small or large amplitude within the patient’s control and range of
motion) (Gross et al., 2010), light massage, deep friction massage, low-level laser, cervico-
scapular exercise, and sham treatments;
4. Outcome measures were pain intensity, pain frequency, pain duration or disability;
5. Design was a randomised controlled trial (RCT).
Unlike the SMT group, the manual therapies group could be comprised of multimodal
interventions. Trials of patients diagnosed with other types of headaches i.e., migraine and/or

tension-type headache or treated primarily with pharmacological interventions were excluded
from this review. Studies that included SMT combined with spinal mobilisation and/or
exercises were also excluded.
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Data Extraction and Synthesis
Four reviewers (JT, IS, TW, DS) independently assessed the risk of bias of each study, using the
Physiotherapy Evidence Database (PEDro) scale, which assesses the internal validity of a RCT (de
Morton, 2009; Maher et al., 2003). Study authors used the rating that PEDro provided and rated
eligible trials not available on the PEDro database (http://www.pedro.org.au). A PEDro score of 7
or greater out of 10 was considered ‘high quality’, while those with a score of 5 or 6 were
considered ‘moderate quality’ and a score of 4 or less ‘poor quality’. Five reviewers (JT, IS, TW,
DS, MF) also independently extracted characteristics of the included studies, as well as means,
standard deviations, and sample sizes using a standardised data extraction form. When there
was insufficient information in trial reports, data were imputed using methods recommended
in the Cochrane Handbook for Systematic Reviews of Interventions. Briefly, we adopted the
standard deviation from the most similar study (J. P. Higgins, 2008). Information on adverse
events was extracted where available.
The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach

was used to evaluate the overall quality of evidence and the strength of the recommendation
(Group, 2004). Briefly, the overall quality of evidence was initially regarded as “High” for RCTs,
but downgraded by 1 level for each of three factors encountered: limitations in the design
(>25% of studies considered a risk of bias - PEDro score <7 points); inconsistency of results
(large heterogeneity between trials - I2> 50%); imprecision (<400 patients in total for each
outcome) (Guyatt et al., 2011). Publication bias was assessed with a funnel plot if more than 10
studies were included in the meta-analyses. Indirectness was not considered for this review
due to the presence of a specific population, relevant outcome measures and direct
comparisons. One reviewer (MF) judged whether these factors were present for each outcome.

The following defined the quality of evidence: (1) high quality - further research is unlikely to
change our confidence in the estimate of effect; (2) moderate quality - further research is likely
to have an important impact on our confidence in the estimate of effect and might change the
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estimate; (3) low quality - further research is likely to have an important impact on our
confidence in the estimate of effect and is likely to change the estimate and (4) very low
quality—we are uncertain about the estimate.
Data synthesis and statistical analysis

Outcome data were extracted for the following time intervals: short-term (>2 weeks but ≤3
months), intermediate term (>3 months but <12 months), and long-term (≥ 12 months) follow up
evaluations. When multiple time points fall within the same category, the one closest to six
weeks for the short-term, six months for the intermediate-term and 12 months for the long-term
were used. When more than one outcome measure was used to assess pain intensity or
disability, the primary outcome measure for the trial was utilised. We also considered the
secondary outcome if the study was adequately powered. All pain and disability outcome
measures used to calculate pooled effects are summarised in Supplementary Table A.
We conducted the meta-analyses using a random effects model and calculated the mean
difference (MD) with 95% confidence intervals (CI) for all point estimates for pain intensity and
disability measures. Both these two outcomes were converted to a common 0 to 100 scale (0 =
no pain or disability to 100 = worst possible pain or disability). Other outcome data reported for
each study, i.e., pain frequency and pain duration were expressed as standardized mean
differences (SMDs) with 95% CIs. The SMD will judge the magnitude of the effect, utilising the
general rules of thumb described by Cohen (J, 1988), that suggest that an SMD of 0.2 represents
a “small” effect, an SMD of 0.5 represents a “medium” effect, and an SMD of 0.8 (or greater)
represents a “large” effect.
MD and SMD were calculated as the difference in means between groups. Heterogeneity was
evaluated by the I2 Statistic, with I2> 30%, I2> 50% and I2> 75% indicating moderate, substantial
and considerable heterogeneity (J. P. T. Higgins & Thompson, 2002). Authors were contacted

for additional and/or missing data. All analyses and output figures were generated using
RevMan5 software ("The Nordic Cochrane Centre. Review Manager (RevMan) [Computer
program]. Version 5.3. Copenhagen: The Cochrane Collaboration; 2014.,").
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Results
Study selection
The electronic search retrieved 1127 individual studies. Citations were screened by title and
abstract and a total of 59 articles were retrieved for evaluation in full text. A total of 7
published papers were included in the meta-analysis (Figure 1).
Study characteristics
From the 7 trials, we included a total of 403 participants with age ranging between 7 and 70
years. Three studies were from the United States (Dunning et al., 2016; Haas et al., 2018; Haas et
al., 2010), 2 from Denmark (Nilsson, 1995; Nilsson et al., 1997), 1 from Germany (Borusiak et al.,
2010) and 1 from Norway (Chaibi et al., 2017). Interventions were conducted in an independent
chiropractic research institution in 2 studies (Nilsson, 1995; Nilsson et al., 1997), outpatient
physical therapy clinics in 1 study(Dunning et al., 2016), chiropractic practices in 1 study (Chaibi
et al., 2017), chiropractic college outpatient clinic in 1 study (Haas et al., 2010), university clinic
and private chiropractic clinics in 1 study (Haas et al., 2018)and at a neuropediatric headache
outpatient clinic in 1 study (Borusiak et al., 2010).
SMT was delivered to the cervical spine (Borusiak et al., 2010; Chaibi et al., 2017; Dunning et al.,
2016; Haas et al., 2018; Haas et al., 2010; Nilsson, 1995; Nilsson et al., 1997), thoracic spine
(Dunning et al., 2016; Haas et al., 2018; Haas et al., 2010) and ribs 1-9 (Dunning et al., 2016).
Other manual therapy interventions were heterogeneous in nature and included: spinal
mobilisation and cranio-cervical flexion exercises (Dunning et al., 2016), light massage (Haas et
al., 2018; Haas et al., 2010) and deep friction massage with laser (Nilsson, 1995; Nilsson et al.,
1997). Additionally, light touch to specific cervical spine segments (Borusiak et al., 2010) and
manipulation at the lateral edge of the scapula and/or the gluteal region (Chaibi et al., 2017)

were respectively considered as sham interventions, and incorporated into other manual
therapies. The characteristics of all included trials are summarized in Table 1.
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Numerous outcome measures were utilised for pain intensity including Visual Analogue Scale
(VAS) (Nilsson, 1995; Nilsson et al., 1997), the Modfied Von Korff Scale (Haas et al., 2010),
Numerical Rating Scale (NRS) (Chaibi et al., 2017; Haas et al., 2018), Numeric Pain Rating Scale
(NPRS) (Dunning et al., 2016), and the Visual/Numerous Analog Scale (VAS/NAS) (Borusiak et al.,
2010). For disability; the Modfied Von Korff Scale (Haas et al., 2010), Neck Disability Index
(NDI)(Dunning et al., 2016), and the Headache Impact test (HIT-6) were utilised (Haas et al.,
2018). For pain frequency; mean of 30 days/month (Chaibi et al., 2017), mean days with
headache in the last 4 weeks (Haas et al., 2018; Haas et al., 2010) and headache days in the week
(Dunning et al., 2016)were used. Finally, for pain duration; mean hours per day(Chaibi et al.,
2017), mean headache hours per day (Nilsson, 1995; Nilsson et al., 1997), headache hours in the
last week (Dunning et al., 2016), headache hours in total (Borusiak et al., 2010), and hours in
years were utilised. Although similar outcomes were assessed, these measurements varied
across studies.
Risk of Bias
The risk of bias assessment (PEDro) of each trial is summarized in Supplementary Table B. The
methodological quality assessment using the PEDro scale (scored out of 10) revealed a mean
score of 6.9 (SD = 0.6). Five studies were considered “high quality” (Borusiak et al., 2010; Chaibi
et al., 2017; Dunning et al., 2016; Haas et al., 2018; Haas et al., 2010) and 2 studies were
considered “moderate quality”(Nilsson, 1995; Nilsson et al., 1997). A key problem item included
blinding of therapists who delivered the therapy, as can be expected for this type of intervention.
Analysis
Short-term Follow-up
Pooling of all included trials for the short-term follow-up revealed “low-quality evidence”
(GRADE) (Table 2), showing a significant, small effect favouring SMT over other manual therapies
for pain intensity (7 studies, I2 = 70%, MD -10.88 [95% CI, -17.94, -3.82]). There is “moderate-

quality evidence” showing a significant, small effect favouring SMT over other manual therapies
for disability (2 studies, I2 = 0%, MD -13.31[95% CI, -18.07, -8.56]). For pain frequency, there is
“moderate-quality evidence” showing a significant, small effect favouring SMT over other manual
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therapies (3 studies, I2 = 0%, SMD -0.35 [95%CI, -0.66 -0.04]), and “low-quality evidence” showing
a non-significant effect for pain duration (3 studies, I2 = 0%, SMD -0.08 [95%CI, -0.47, 0.32])
(Figure 2A).
Intermediate-term Follow-up
At intermediate follow-up, there was "low-quality evidence" showing a non-significant difference
between SMT and other manual therapies for pain intensity (3 studies, I2 = 60%, MD -9.77 [-24.21
to 4.68]) and "moderate-quality evidence" showing a significant, small effect favouring SMT over
other manual therapies for pain frequency (3 studies, I2 = 0%, SMD -0.32 [-0.63 to -0.00]) (Figure
2B). We were unable to pool results for disability and pain duration in the intermediate-term due
to a lack of data reported.
Long-term Follow-up
At long-term follow-up, there was "low-quality evidence" showing a non-significant difference
between SMT and other manual therapies for pain intensity (2 studies, I2 = 0%, MD -0.76 [-5.89
to 4.37]) and "moderate-quality evidence" showing a small, but non-significant effect, favouring
SMT over other manual therapies for pain frequency (2 studies, I2 = 7%, SMD -0.37 [-0.84 to
0.10]) (Figure 2C). We did not pool results for disability and pain duration in the long-term due to
a lack of data reported.
Adverse Effects
Three studies did not report on participants who experienced adverse events (Haas et al., 2010;
Nilsson, 1995; Nilsson et al., 1997). In the remaining studies, one trial reported hot skin and
dizziness with no significant between-group differences (Borusiak et al., 2010). A single trial
reported mild and transient (local) tenderness and tiredness on the day of treatment (Chaibi et
al., 2017). Another study reported no major adverse events for either group, but did not collect
any data on minor adverse events (Dunning et al., 2016). The remaining trial reported minor

adverse effects, including: neck pain or soreness, stiffness, transient upper extremity
pain/tingling, increased headache intensity, nausea and dizziness (Haas et al., 2018).
Supplementary Table C summarises adverse events reported in all trials.
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Discussion
This systematic review and meta-analysis demonstrated that SMT provides significant, small
short-term effects for pain intensity, frequency and disability but not pain duration among
people suffering from CGHA. Effect sizes in our meta-analysis generally reduced over the
intermediate and long-term follow up periods. The lack of high-quality evidence utilising the
GRADE approach creates some uncertainly in these results.
Our findings are generally in agreement with previous contemporary systematic reviews
regarding the efficacy of manual therapies for CGHA (Chaibi & Russell, 2012; Coelho et al., 2019;
Garcia et al., 2016; Racicki et al., 2013). Our review adds to the existing literature by including a
greater number of eligible trials in the pooled analysis. In contrast to other reviews (Chaibi &
Russell, 2012; Coelho et al., 2019; Garcia et al., 2016; Racicki et al., 2013), our review isolated
SMT as a single modality and found statistically significant differences favouring SMT over other
manual therapies in the short-term. Few other reviews on the topic have reported the effect
sizes for key outcomes (Racicki et al., 2013). Another interesting finding from our results was that
SMT confers small benefits in the intermediate term for CGHA pain frequency, with the
magnitude of effect remaining both small and statistically significant throughout this follow up
period (SMD -0.32 [-0.63 to -0.00] P = 0.05). Headache frequency is considered the most
important primary measure in efficacy studies for headache, according to the IHS guidelines for
controlled trials (Bendtsen et al., 2009).
Although our review identified statistically significant differences between SMT and other
manual therapies in the short-term, it is important to consider our findings in light of clinically
meaningful effects. Minimal clinically important change (MCID) or the smallest worthwhile effect
(Kamper, 2019a), refers to the smallest difference that patients perceive as beneficial with

respect to the treatment they receive. By reporting the estimate of the size of effects in our
review (as opposed to just the presence of effects), we can further evaluate whether these
treatment effects are likely to be large enough to be considered important for patients.
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Currently, there is little evidence on what defines the smallest worthwhile effect of interventions
for CGHA. A recent analysis of psychometric properties for CGHA patient outcomes, determined
a MCID threshold for self-reported pain intensity of 2.5 points on the 0-10 Numeric Pain Rating
Scale and 5.5 points on the 0-50 Neck Disability Index Scale at the short-term follow up (Young et
al., 2019). Although these new CGHA estimates (which utilised the CHISG diagnostic criteria) help
determine a threshold for clinically meaningful difference, it remains unknown whether some
patients may consider the small, superior short-term effects in our review as clinically
worthwhile. For instance, a treatment effect which favoured SMT for pain intensity in the short-
term (MD -10.88 [95% CI, -17.94, -3.82] P = 0.003), may be considered too small to be
worthwhile. Yet the treatment effect of disability in the short-term (MD -13.31 [95% CI, -18.07, -
8.56] P = <0.00001) may justify the effort to seek SMT for CGHA.
Given that there is no universal agreement on the size of a worthwhile effect (Kamper, 2019b),
clinicians in practice can discuss the estimated effect with patients, who can then set their own
individual ‘cut off’ points as the smallest worthwhile effect. In doing so, the patient must
consider and balance several factors related to undertaking an intervention, including perceived
benefits and potential risks associated with treatment, personal expectations, duration of
treatment, and related costs – all which are incorporated into their treatment decision making
process (Herbert, 2019; Kamper, 2019a). Further to these considerations is the paucity of
research evidence for the relief of CGHA from drug treatments as well as other far more invasive
available treatments (Anthony, 2000; Zhang et al., 2011; Zhou et al., 2010).
A recently published evidence-based guideline for the non-pharmacological management of

headaches associated with neck pain, recommends the use of SMT, spinal mobilisation or cranio-
cervical-scapula exercises for CGHA management (Côté et al., 2019). Importantly, this guideline
did not recommend combining these therapeutic modalities (Côté et al., 2019). In line with this

guideline recommendation, our study findings suggest SMT, in isolation, provides comparatively
superior, small short-term benefits to CGHA pain intensity, frequency and disability over other
manual therapies. Communicating such findings may be valuable in the shared decision-making
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process between practitioners and patients, when considering treatment options for CGHA. In
doing so, clinicians need to discuss any potential treatment benefits i.e., the positive impacts of
SMT on the quality-of-life of those with CGHA (Suijlekom et al., 2003), as well as the potential
harms, i.e., mild-to-moderate adverse events generally associated with SMT (Carnes et al., 2010).
Accordingly, this process helps ensure clinicians support patients in choosing treatment options
that best aligns with patient preferences and values (Hoffmann et al., 2019).
This systematic review and meta-analysis provides an up-to-date summary of the impact of SMT
among CGHA sufferers. Other strengths include a comprehensive search of numerous electronic
databases, and most of the trials included were of high methodological quality (mean PEDro
Score of 7). Furthermore, we utilised the GRADE system to appraise the overall quality of
evidence. Our recommendations were based on the pooled treatment effects and provided
clinically interpretable estimates (where possible), thus assisting clinicians and patients as to
whether they would consider SMT for CGHAs as meaningful or important.
A limitation of the current literature was the limited number of trials (n=7) with a relatively small
sample size, ranging from 4 to 63 patients. Therefore, the overall quality of the evidence for all
meta-analyses were downgraded for reasons of imprecision as less than 400 patients were
included in the analysis (Guyatt et al., 2011). Within our pooled studies, there was between-trial
heterogeneity (I2 = 70%) for the short-term pain intensity outcome. In general, the considerable
heterogeneity in our study is likely due to the use of different outcome measures and
methodologies. One example is the different diagnostic inclusion criteria utilised for CGHA
diagnosis as assessed by the practitioners (Avijgan et al., 2019). While published diagnostic
criteria from the CHISG and IHS are similar, they also vary and can therefore result in patient
presentation variability with respect to study eligibility criteria. For example, IHS criteria includes
headache with a temporal relationship (increasing and decreasing) with neck pain with no clear
guidance for how this is determined (Fredriksen et al., 2015b). Unlike the IHS, CHISG includes

pain starting posteriorly moving anteriorly; unilateral head pain, without side shift and diffuse
shoulder and/or arm pain as criteria (Fredriksen et al., 2015b). More generally, neither IHS or
CHISG provide clear guidance on the magnitude or direction of the neck provocation needed to
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stimulate headache or the extent of the loss of cervical motion needed for a diagnosis
(Fredriksen et al., 2015b). Furthermore, all studies within our review did not fully adopt the
diagnostic criteria, i.e., certain IHS criterion was not relevant to the clinical trial (Haas et al.,
2018), or further subgrouping beyond the IHS was required (Borusiak et al., 2010). Some studies
excluded the radiographic criterion from the IHS (Haas et al., 2010; Nilsson, 1995; Nilsson et al.,
1997) or excluded nerve blockage from the CHISG (Chaibi et al., 2017; Dunning et al., 2016). In
our review, the IHS criteria was utilised in 5 studies (Borusiak et al., 2010; Haas et al., 2018; Haas
et al., 2010; Nilsson, 1995; Nilsson et al., 1997), while the CHISG was utilised in 2 studies (Chaibi
et al., 2017; Dunning et al., 2016). A sensitivity analysis according the different CGHA diagnostic
criteria utilised continued to show significant, small effects favouring SMT over other manual
therapies, with respect to pain intensity in the short-term for the IHS (5 studies, I2 = 31%, MD -
7.32 [95% CI, -12.62, -2.02]) and the CHISG (2 studies, I2 = 0%, MD -19.52 [95% CI, -26.22, -12.82])
respectively.
It is also likely that some patients with the diagnosis of CGHA, may have co-occurring migraine
and/or tension-type headache (Knackstedt et al., 2010). This is problematic for clinicians (and
researchers) in determining the exact diagnosis and therefore the most appropriate treatment
strategy to manage CGHA specifically (Avijgan et al., 2020). Ultimately, the diagnosis of CGHA
may only be demonstrable in a definitive manner, by way of anaesthetic blockade procedures
(Avijgan et al., 2020), which was not available in our included trials. Another limitation includes
the different forms of SMT techniques that were incorporated within the included studies and
the treatment frequency varied between trials and/or was not always clearly defined. In
addition, other interventions were sometimes also used in conjunction with the other manual
therapy study groups. Only English language studies published in peer-reviewed journals were
included and it was not possible to carry out all planned analyses due to insufficient data
available within studies.

While this review provides clinically interpretable estimates, future trials that evaluate the
intermediate- to long-term impact of SMT for CGHAs are needed. These forthcoming trials should
be adequately powered and utilise the current CGHA diagnostic criteria. Future trials should also
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reflect recommendations from the most recent guidelines with respect to SMT for CGHA (Côté et
al., 2019). Additionally, trials should include a cost-effectiveness analysis and patient subgrouping
to better determine the profile of those with CGHA who are more likely to benefit from SMT.
Although differential diagnosis can be challenging, there is a need for trial designs to effectively
isolate CGHA participants from those with co-occurring migraine and/or tension-type headache.
Conclusion
Results from this systematic review and meta-analysis suggests that SMT provides significant,
small effects in the short-term for CGHA pain intensity, frequency, and disability but not
duration. Effect sizes generally reduce over the intermediate term, while the long-term impact of
SMT was not significant. Importantly, high-quality evidence in this field is needed. Nevertheless,
findings from this review can help to guide clinicians and patients when considering SMT as an
intervention for CGHA.
Author contributions
MF, CM, and ABu were involved in study conception and design along with acquisition,
analysis and interpretation of data. All authors discussed the results, revised and commented the
manuscript. All authors approved the final version to be published.
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Select Participants in Randomised Controlled Trials of Interventions Used to Treat
Cervicogenic Headache. Headache: The Journal of Head and Face Pain.
Accepted Article
Avijgan, M., Thomas, L. C., et al. (2020). A Systematic Review of the Diagnostic Criteria Used to
Select Participants in Randomised Controlled Trials of Interventions Used to Treat
Cervicogenic Headache. Headache: The Journal of Head and Face Pain, 60(1), 15-27.
doi:10.1111/head.13719
Barmherzig, R., & Kingston, W. (2019). Occipital Neuralgia and Cervicogenic Headache: Diagnosis
and Management. Current Neurology and Neuroscience Reports, 19(5), 20.
doi:10.1007/s11910-019-0937-8
Bendtsen, L., Bigal, M. E., et al. (2009). Guidelines for controlled trials of drugs in tension-type
headache: second edition. Guidelines for controlled trials of drugs in tension-type
headache: second edition. Cephalalgia, 0(0). doi:10.1111/j.1468-2982.2009.01948.x
Bogduk, N. (1992). The anatomical basis for cervicogenic headache. Journal of Manipulative and
Physiological Therapeutics, 15(1), 67-70.
Bogduk, N. (2014). The Neck and Headaches. Neurologic Clinics, 32(2), 471-487.
doi:10.1016/j.ncl.2013.11.005
Bogduk, N., & Govind, J. (2009). Cervicogenic headache: an assessment of the evidence on
clinical diagnosis, invasive tests, and treatment. The Lancet Neurology, 8(10), 959-968.
doi:https://doi.org/10.1016/S1474-4422(09)70209-1
Borusiak, P., Biedermann, H., et al. (2010). Lack of Efficacy of Manual Therapy in Children and
Adolescents With Suspected Cervicogenic Headache: Results of a Prospective,
Randomized, Placebo-Controlled, and Blinded Trial. Headache: The Journal of Head and
Face Pain, 50(2), 224-230. doi:10.1111/j.1526-4610.2009.01550.x
Carnes, D., Mars, T. S., et al. (2010). Adverse events and manual therapy: A systematic review.
Manual Therapy, 15(4), 355-363. doi:https://doi.org/10.1016/j.math.2009.12.006
Chaibi, A., Knackstedt, H., et al. (2017). Chiropractic spinal manipulative therapy for cervicogenic
headache: a single-blinded, placebo, randomized controlled trial. BMC Research Notes,
10(1), 310. doi:10.1186/s13104-017-2651-4

Chaibi, A., & Russell, M. B. (2012). Manual therapies for cervicogenic headache: a systematic
review. The Journal of Headache and Pain, 13(5), 351-359. doi:10.1007/s10194-012-0436-
7
Accepted Article
Coelho, M., Ela, N., et al. (2019). The effectiveness of manipulation and mobilization on pain and
disability in individuals with cervicogenic and tension-type headaches: a systematic
review and meta-analysis. Physical Therapy Reviews, 24(1-2), 29-43.
doi:10.1080/10833196.2019.1572963
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associated with neck pain: A clinical practice guideline from the Ontario protocol for
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Dunning, J. R., Butts, R., et al. (2016). Upper cervical and upper thoracic manipulation versus
mobilization and exercise in patients with cervicogenic headache: a multi-center
randomized clinical trial. BMC Musculoskeletal Disorders, 17(1), 64. doi:10.1186/s12891-
016-0912-3
Fredriksen, T. A., Antonaci, F., et al. (2015a). Cervicogenic headache: too important to be left un-
diagnosed. The Journal of Headache and Pain, 16(1), 6. doi:10.1186/1129-2377-16-6
Fredriksen, T. A., Antonaci, F., et al. (2015b). Cervicogenic headache: too important to be left un-
diagnosed. The Journal of Headache and Pain, 16, 6-6. doi:10.1186/1129-2377-16-6
Garcia, J. D., Arnold, S., et al. (2016). Mobilization and Manipulation of the Cervical Spine in
Patients with Cervicogenic Headache: Any Scientific Evidence? Frontiers in Neurology,
7(40). doi:10.3389/fneur.2016.00040
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Manual Therapy, 15(4), 315-333. doi:https://doi.org/10.1016/j.math.2010.04.002
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imprecision. Journal of clinical epidemiology, 64(12), 1283-1293.
doi:https://doi.org/10.1016/j.jclinepi.2011.01.012
Accepted Article
Haas, M., Bronfort, G., et al. (2018). Dose-response and efficacy of spinal manipulation for care of
cervicogenic headache: a dual-center randomized controlled trial. The Spine Journal,
18(10), 1741-1754. doi:https://doi.org/10.1016/j.spinee.2018.02.019
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chronic cervicogenic headache: a pilot randomized controlled trial. The Spine Journal,
10(2), 117-128. doi:https://doi.org/10.1016/j.spinee.2009.09.002
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misleading and mostly unnecessary. Journal of physiotherapy.
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in Medicine, 21(11), 1539-1558. doi:10.1002/sim.1186
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physiotherapy practice. Physiotherapy. doi:https://doi.org/10.1016/j.physio.2019.08.012
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Lawrence Erlbaum Associates: Routledge.
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Meaningfulness: Linking Evidence to Practice. Journal of Orthopaedic & Sports Physical
Therapy, 49(7), 559-560. doi:10.2519/jospt.2019.0704
Kamper, S. J. (2019b). Showing confidence (intervals). Brazilian journal of physical therapy, 23(4),
277-278. doi:10.1016/j.bjpt.2019.01.003

Knackstedt, H., Bansevicius, D., et al. (2010). Cervicogenic headache in the general population:
The Akershus study of chronic headache. Cephalalgia, 30(12), 1468-1476.
doi:10.1177/0333102410368442
Accepted Article
Liberati, A., Altman, D. G., et al. (2009). The PRISMA statement for reporting systematic reviews
and meta-analyses of studies that evaluate health care interventions: explanation and
elaboration. PLoS medicine, 6(7), e1000100.
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randomized controlled trials. Physical therapy, 83(8), 713-721.
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4610.1998.3806442.x
Accepted Article
Suijlekom, H. A. v., Lamé, I., et al. (2003). Quality of Life of Patients With Cervicogenic Headache:
A Comparison With Control Subjects and Patients With Migraine or Tension-type
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doi:https://doi.org/10.1016/j.math.2005.04.007

Table 1. Study characteristics
Accepted Article
Study Types of Pedro Participants Experimental Control Group Follow-up & Results
Study score Group outcome
measures
Borusiak Multicentre, 7/10 n = 52 n = 24 n = 28 placebo 2 months No statistical significance
et al. Placebo- participants received manipulation, between the 2 groups
(2010) controlled (Age 7-15 cervical light touch of Headache
RCT years) manipulative cervical spine duration,
treatment intensity and
medication
Chaibi et Single 7/10 n = 12 n = 4 received n = 4 received 3, 6 and 12 Participants who received
al. (2017) blinded participants cervical sham months spinal manipulative and
placebo RCT (Age 18 -70) manipulative manipulation, n sham both improved for
treatment = 4 used as a Headache headache frequency at
control with no duration, all-time points
manipulation intensity index
and primary
of frequency
Dunning Multicentre, 8/10 n = 110 n = 58 n = 52 received 1 week, 4 Participants who received
et al. RCT participants received mobilization weeks, 3 cervical and thoracic
(2016) (Mean age cervical and and exercise months manipulative treatment
of 35) thoracic had better outcome
manipulative Headache measures from week 1 to 3
therapy duration, months follow up. Spinal
intensity and manipulation was more
frequency effective than spinal
mobilization
Haas et Two-site, 7/10 n = 256 n = 63 n = 64 received 6,12,24,39 Participants in both groups
al. open label participants received 18 18 light and 52 weeks improved, however those
(2018) RCT (Mean age cervical and massage who received spinal
of 41) upper sessions, n = 65 Headache manipulative therapy had
thoracic received 6 duration, more significant reductions
manipulative manipulative intensity and in the number of
therapy therapy and 12 frequency, in headache days, i.e.,
massage addition to headache days were
session, n = 64 perceived reduced by about half
received 12 improvement,
manipulative medication
therapy and 6 use, and
massage patient
sessions satisfaction
Haas et 2x2 Balance 7/10 n = 80 n = 20 n = 20 received 4,8,16 and 20 There were clinically

al. factorial participants received 5 mins of moist via phone, 12 important and statistically
(2010) design RCT (Mean age cervical and heat pack and and 24 weeks significant differences
Accepted Article
36) thoracic 5 minutes of via mail which favoured spinal
manipulative light massage manipulation over light
therapy for 16 for 16 sessions, Headache massage for pain and
sessions n = 20 received and neck disability
8 manipulative pain
sessions and frequency,
attention intensity,
control physical medication
examination, n use and
= 20 received disability
light massage
for 8 sessions
and attention
control physical
examination
Nilsson et RCT with 6/10 n = 38 n = 20 n = 18 received Changes Participants in the spinal
al. blinded participants received soft tissue work observed manipulation group
(1995) observer (Age 20-57) upper and (laser upper from week 2 showed improvements in
lower cervical cervical area to week 6 all outcomes, although the
spinal and deep differences between the
adjustments friction Headache treatment groups did not
for 3 weeks massage in duration, reach statistical
lower cervical intensity and significance
area) medication
usage
Nilsson et RCT with 6/10 n = 53 n = 28 n = 25 received Changes Participants in the spinal
al. blinded (Age 20-60) received laser in the observed manipulation group
(1997) observer upper and upper cervical from week 1 showed improvements in
lower cervical area and deep to week 5 headache duration,
spinal friction intensity and medication
adjustments massage in the Headache usage
for 3 weeks lower cervical intensity
area for 3 and
weeks medication
usage

ccepted Article
Table 2: Summary of Outcome Findings and Quality of Evidence Assessment (GRADE)
Studies Quality of No. of Effect* Quality
(References) Evidence Participants
by Assessment
Outcome (GRADE)
Risk of Bias Inconsistency Imprecision Indirectness Publication SMT Control MD or SMD
2
(design - limitation) (I >50%) (<400) bias Group Group (95% CI)
Short-term
Intensity, 7 Serious limitation ‡ Serious No serious - - 209 194 -10.88 (-17.94 to -3.82) Low
studies (-1) inconsistency § imprecision ¶ ∞
(-1)
Disability, 2 No Serious limitation No serious Serious - - 72 67 -13.31 (-18.07 to -8.56) Moderate
studies ‡ inconsistency § imprecision (-1) ∞
¶
Frequency, 3 No Serious limitation No serious Serious - - 83 80 -0.35 (-0.66 to -0.04) Moderate
studies ‡ inconsistency § imprecision (-1) £
¶
Duration, 3 Serious limitation ‡ No serious Serious - - 52 47 -0.08 (-0.47 to 0.32) Low
studies (-1) inconsistency § imprecision (-1) £
¶
Intermediate
Intensity, 3 No Serious limitation Serious Serious - - 81 76 -9.77 (-24.21 to 4.68) Low
(-1) ¶

ccepted Article
Frequency, 3
studies
No Serious limitation
‡
No serious
inconsistency §
Serious
imprecision (-1)
- - 81 76 -0.32 (-0.63 to -0.00)
£
Moderate
¶
Long-term
Intensity, 2 No Serious limitation No serious Serious - - 64 56 -0.76 (-5.89 to 4.37) Moderate
¶
Frequency, 2 No Serious limitation No serious Serious - - 64 56 -0.37 (-0.84 to 0.10) Moderate
studies ‡ inconsistency § imprecision (-1) £
¶
SMT = Spinal Manipulation Group

MD = weighted mean difference
SMD – Standardized mean difference
∞ = MD
£ = SMD
* Negative values (-) favour SMT group.
‡ Limitation in study design: more than 25% of participants from studies with low methodological quality (PEDro score <7 points)
§ Inconsistency of results: substantial I2 (>50%)
¶Imprecision: Fewer than 400 participants for each outcome
Indirectness: this review evaluated a specific population with CGHA – not measured
Publication bias: there were less than 10 studies included in the meta-analyses for a funnel plot – not measured

Records identified through 5
database searches
Accepted Article Medline (204)
Mantis (68)
Embase (606)
Cochrane Library (206)
Identification
PEDro (43) Additional records identified

(n=1,127) through other sources
(n=0)
Records after duplicates removed

(n=783)
Screening
Records screened Records excluded by title

(n = 778) (n = 719)
Full-text articles assessed Full-text articles excluded

for eligibility (n=52)
Eligibility
(n=59) Reasons:
Spinal mobilisation (n=9)
Commentary (n=10)
Systematic review (n=3)
Studies included in Double reporting (n=2)
qualitative synthesis Protocol (n=8)
(n=7) Not in English (n=2)
No control group (n=1)
Conference abstract (n=2)
Included
Different intervention (n=15)

Studies included in
quantitative synthesis
(meta-analysis)
(n=7)
cepted Articl
Headache Intensity, short-term
cepted Articl
Headache Disability, short-term
cepted Articl
Headache Frequency – short-term
cepted Articl
Headache Duration – short-term
cepted Articl
Intermediate-term Headache Intensity
cepted Articl
Intermediate-term Headache Frequency
cepted Articl
Long-term Headache Intensity
cepted Articl
Long-term Headache Frequency
Appendix 1 Search strategy December 18, 2019
Accepted Article
Medline
1 randomized controlled trial.pt.
2 controlled clinical trial.pt.
3 randomized.ab.
4 placebo.ab.
5 drug therapy.fs.
6 randomly.ab.
7 trial.ab.
8 groups.ab.
9 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8
10 exp animals/ not humans.sh.
11 9 not 10
12 exp Post-Traumatic Headache/
13 exp Neck Pain/
14 cervicogenic headache.mp.
15 12 or 13 or 14
16 exp Manipulation, Spinal/
17 spinal manipulation.mp.
18 exp Manipulation, Chiropractic/
19 chiropractic manipulation.mp.
20 exp Manipulation, Osteopathic/
21 osteopathic manipulation.mp.
22 chiropractic adjustment.mp.
23 16 or 17 or 18 or 19 or 20 or 21 or 22
24 11 and 15

25 23 and 24
Accepted Article
Embase
1 Clinical trial/
2 Randomized controlled trial/
3 Randomization/
4 Single blind procedure/
5 Double blind procedure/
6 Crossover procedure/
7 Placebo/
8 Randomi?ed controlled trial$.tw.
9 Rct.tw.
10 Random allocation.tw.
11 Randomly allocated.tw.
12 Allocated randomly.tw.
13 (allocated adj2 random).tw.
14 Single blind$.tw.
15 Double blind$.tw.
16 ((treble or triple) adj blind$).tw.
17 Placebo$.tw.
18 Prospective study/

19 or/1-18
20 Case study/
Accepted Article
21 Case report.tw.
22 Abstract report/ or letter/
23 or/20-22
24 19 not 23
25 exp posttraumatic headache/
26 exp secondary headache/
27 neck pain/
28 cervicogenic headache.tw.
29 25 or 26 or 27 or 28
30 24 and 29
31 exp spine manipulation/
32 chiropractic manipulation/
33 osteopathic manipulation/
34 exp manipulative medicine/
35 spinal manipulation.tw.
36 chiropractic manipulation.tw.
37 31 or 32 or 33 or 34 or 35 or 36
38 30 and 37
Mantis
# Searches
randomized controlled trial.mp. [mp=title, abstract, original title, name of substance word, subject
1 heading word, floating sub-heading word, keyword heading word, organism supplementary concept
word, protocol supplementary concept word, rare disease supplementary concept word, unique

identifier, synonyms]
controlled clinical trial.mp. [mp=title, abstract, original title, name of substance word, subject heading
Accepted Article
word, floating sub-heading word, keyword heading word, organism supplementary concept word,
2
protocol supplementary concept word, rare disease supplementary concept word, unique identifier,
synonyms]
random*.mp. [mp=title, abstract, original title, name of substance word, subject heading word, floating
3 sub-heading word, keyword heading word, organism supplementary concept word, protocol
supplementary concept word, rare disease supplementary concept word, unique identifier, synonyms]
RCT.mp. [mp=title, abstract, original title, name of substance word, subject heading word, floating sub-
4 heading word, keyword heading word, organism supplementary concept word, protocol supplementary
concept word, rare disease supplementary concept word, unique identifier, synonyms]
placebo.mp. [mp=title, abstract, original title, name of substance word, subject heading word, floating
5 sub-heading word, keyword heading word, organism supplementary concept word, protocol
trial.mp. [mp=title, abstract, original title, name of substance word, subject heading word, floating sub-
6 heading word, keyword heading word, organism supplementary concept word, protocol supplementary
concept word, rare disease supplementary concept word, unique identifier, synonyms]
7 1 or 2 or 3 or 4 or 5 or 6
post-traumatic headache.mp. [mp=title, abstract, original title, name of substance word, subject heading
8
synonyms]
cervicogenic headache.mp. [mp=title, abstract, original title, name of substance word, subject heading
9
synonyms]
chronic neck pain.mp. [mp=title, abstract, original title, name of substance word, subject heading word,
10
floating sub-heading word, keyword heading word, organism supplementary concept word, protocol

11 8 or 9 or 10
Accepted Article
spinal manipulation.mp. [mp=title, abstract, original title, name of substance word, subject heading word,
12 floating sub-heading word, keyword heading word, organism supplementary concept word, protocol
manipulation, spinal.mp. [mp=title, abstract, original title, name of substance word, subject heading
13
synonyms]
spinal manipulative therapy.mp. [mp=title, abstract, original title, name of substance word, subject
heading word, floating sub-heading word, keyword heading word, organism supplementary concept
14
word, protocol supplementary concept word, rare disease supplementary concept word, unique
identifier, synonyms]
cervical manipulation.mp. [mp=title, abstract, original title, name of substance word, subject heading
15
synonyms]
chiropractic manipulation.mp. [mp=title, abstract, original title, name of substance word, subject heading
16
synonyms]
manipulation, chiropractic.mp. [mp=title, abstract, original title, name of substance word, subject heading
17
synonyms]
osteopathic manipulation.mp. [mp=title, abstract, original title, name of substance word, subject heading
18 word, floating sub-heading word, keyword heading word, organism supplementary concept word,

synonyms]
manipulation, osteopathic.mp. [mp=title, abstract, original title, name of substance word, subject heading
Accepted Article
19
synonyms]
chiropractic adjustment.mp. [mp=title, abstract, original title, name of substance word, subject heading
20
synonyms]
spinal adjustment.mp. [mp=title, abstract, original title, name of substance word, subject heading word,
21 floating sub-heading word, keyword heading word, organism supplementary concept word, protocol
22 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21
23 7 and 11
24 22 and 23
Cochrane Library
ID Search
#1 MeSH descriptor: [Post-Traumatic Headache] explode all trees
#2 cervicogenic headache
#3 MeSH descriptor: [Neck Pain] explode all trees
#4 #1 OR #2 OR #3
#5 MeSH descriptor: [Manipulation, Spinal] explode all trees
#6 spinal manipulation
#7 spinal manipulative therapy
#8 cervical manipulation
#9 chiropractic manipulation

#10 MeSH descriptor: [Manipulation, Chiropractic] explode all trees
#11 osteopathic manipulation

Accepted Article
#12 MeSH descriptor: [Manipulation, Osteopathic] explode all trees
#13 chiropractic adjustment
#14 spinal adjustment
#15 #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14
#16 #4 AND #15
PEDro
1. Abstract/title: cervicogenic headache
2. Method: clinical trial
When searching match all search terms (AND)

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Spinal manipulation for the management of cervicogenic headache: a systematic review and

Corresponding author email: matthew.fernandez@mq.edu.au

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What does this study add?

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5. Design was a randomised controlled trial (RCT).

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The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach

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Data synthesis and statistical analysis

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A recently published evidence-based guideline for the non-pharmacological management of

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SMT = Spinal Manipulation Group

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PEDro (43) Additional records identified

Records after duplicates removed

Records screened Records excluded by title

Full-text articles assessed Full-text articles excluded

Different intervention (n=15)

2 controlled clinical trial.pt.

10 exp animals/ not humans.sh.

12 exp Post-Traumatic Headache/

13 exp Neck Pain/

16 exp Manipulation, Spinal/

18 exp Manipulation, Chiropractic/

20 exp Manipulation, Osteopathic/

This article is protected by copyright. All rights reserved

2 Randomized controlled trial/

4 Single blind procedure/

5 Double blind procedure/

8 Randomi?ed controlled trial$.tw.

13 (allocated adj2 random).tw.

16 ((treble or triple) adj blind$).tw.

This article is protected by copyright. All rights reserved

22 Abstract report/ or letter/

25 exp posttraumatic headache/

26 exp secondary headache/

31 exp spine manipulation/

34 exp manipulative medicine/

This article is protected by copyright. All rights reserved

This article is protected by copyright. All rights reserved

This article is protected by copyright. All rights reserved

#1 MeSH descriptor: [Post-Traumatic Headache] explode all trees

#3 MeSH descriptor: [Neck Pain] explode all trees

#5 MeSH descriptor: [Manipulation, Spinal] explode all trees