The Quality of Reports on Cervical Arterial Dissection following Cervical Spinal Manipulation

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Abstract

Cervical artery dissection (CAD) and stroke are serious harms that are sometimes associated with cervical spinal manipulation therapy (cSMT). Because of the relative rarity of these adverse events, studying them prospectively is challenging. As a result, systematic review of reports describing these events offers an important opportunity to better understand the relation between adverse events and cSMT. Of note, the quality of the case report literature in this area has not yet been assessed. 1) To systematically collect and synthesize available reports of CAD that have been associated with cSMT in the literature and 2) assess the quality of these reports. A systematic review of the literature was conducted using several databases. All clinical study designs involving CADs associated with cSMT were eligible for inclusion. Included studies were screened by two independent reviewers for the presence/absence of 11 factors considered to be important in understanding the relation between CAD and cSMT. Overall, 43 articles reported 901 cases of CAD and 707 incidents of stroke reported to be associated with cSMT. The most common type of stroke reported was ischemic stroke (92%). Time-to-onset of symptoms was reported most frequently (95%). No single case included all 11 factors. This study has demonstrated that the literature infrequently reports useful data toward understanding the association between cSMT, CADs and stroke. Improving the quality, completeness, and consistency of reporting adverse events may improve our understanding of this important relation.

Full-text

Available from: Shari Wynd
The Quality of Reports on Cervical Arterial Dissection
following Cervical Spinal Man ipulation
Shari Wynd
1
*, Michael Westaway
2
, Sunita Vohra
3,4
, Greg Kawchuk
5
1 Texas Chiropractic College, Pasadena, Texas, United States of America, 2 Lifemark Health, University of Alberta, Calgary, Alberta, Canada, 3 Department of Pediatrics,
Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada, 4 Complementary and Alternative Research and Education Program, Pediatric
Complementary and Alternative Medicine Research and Education Network, Alberta Innovates-Health Solutions, Edmonton, Alberta, Canada, 5 Department of Physical
Therapy, University of Alberta, Edmonton, Alberta, Canada
Abstract
Background:
Cervical artery dissection (CAD) and stroke are serious harms that are sometimes associated with cervical
spinal manipulation therapy (cSMT). Because of the relative rarity of these adverse events, studying them prospectively is
challenging. As a result, systematic review of reports describing these events offers an important opportunity to better
understand the relation between adverse events and cSMT. Of note, the quality of the case report literature in this area has
not yet been assessed.
Purpose:
1) To systematically collect and synthesize available reports of CAD that have been associated with cSMT in the
literature and 2) assess the quality of these reports.
Methods:
A systematic review of the literature was conducted using several databases. All clinical study designs involving
CADs associated with cSMT were eligible for inclusion. Included studies were screened by two independent reviewers for
the presence/absence of 11 factors considered to be important in understanding the relation between CAD and cSMT.
Results:
Overall, 43 articles reported 901 cases of CAD and 707 incidents of stroke reported to be associated with cSMT. The
most common type of stroke reported was ischemic stroke (92%). Time-to-onset of symptoms was reported most frequently
(95%). No single case included all 11 factors.
Conclusions:
This study has demonstrated that the literature infrequently reports useful data toward understanding the
association between cSMT, CADs and stroke. Improving the quality, completeness, and consistency of reporting adverse
events may improve our understanding of this important relation.
Citation: Wynd S, Westaway M, Vohra S, Kawchuk G (2013) The Quality of Reports on Cervical Arterial Dissection following Cervical Spinal Manipulation. PLoS
ONE 8(3): e59170. doi:10.1371/journal.pone.0059170
Editor: Jean-Claude Baron, University of Cambridge, United Kingdom
Received July 23, 2012; Accepted February 13, 2013; Published March 20, 2013
Copyright: ß 2013 Wynd et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: Greg Kawchuk receives salary support from the Canada Research Chairs program. Sunita Vohra receives salary support from Alberta Innovate s-Health
Solutions. Training support for Shari Wynd was provided by the Alberta Canadian Institutes of Health Research (CIHR) Training Program in Bone and Joint Health.
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: swynd@txchiro.edu
Introduction
In the area of harms reporting, one topic that has received
significant attention is cervical spinal manipulation therapy
(cSMT), an intervention most often administered by chiropractors
[1,2] to treat musculoskeletal complaints of the head and neck [3]
including headaches [4]. If harms are associated with cSMT, they
most commonly involve additional head and neck pain [2]. While
these adverse events tend to be self-limiting [2], more serious
adverse events have been reported such as neurovascular sequelae
and stroke. More specifically, injuries such as cervical artery
dissection (CAD), whether vertebral, internal carotid, or vertebro-
basilar, have been reported to be associated with Csmt [5–7].
Although this subset of adverse events appears to occur
infrequently [1,8,9], understanding the relation between CADs,
stroke and cSMT is important given the medical [7], societal [1],
economic [9], and legal [8] implications of any event leading to
cerebrovascular compromise.
While the reporting of rare events occurs frequently in larger
studies (such as randomized control trials (RCTs)), the event is
often not reported with sufficient details. Furthermore, systematic
reviews where harms have been reported often exclude non-RCTs
[10], which can minimize useful information about the benefit-to-
harm ratio associated with treatment. Given these circumstances,
harms reporting often occurs through community-based passive
surveillance, which is well known for under-reporting. Despite this
limitation, the majority of emerging harms data still arise from
case reports, making the quality of these reports essential.
Recognizing this, the Cochrane Adverse Effects Methods Group
[10] has recommended that when harms are infrequent,
systematic reviews should include non-RCT study designs; an
approach that requires high quality reporting of case materials to
allow for meaningful interpretation. As the majority of literature
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that describes adverse associated with cSMT are case reports
[5,11], and their inclusion in systematic reviews is encouraged, it is
important to assess the quality of reporting of this body of
literature.
Objective
To systematically collect and synthesize reports of CAD
associated with cSMT and assess reporting quality.
Search Strategy
The following electronic databases were searched between
January 2001 to January 2011: MEDLINE, CINAHL, ALT
HealthWatch, AMED, and EMBASE. The search strategy for
these databases including limits used and Boolean operators are
presented in Table 1. Specific inclusion criteria for this review are:
Study design: All clinical study designs.
Population: Adults and children of any gender.
Intervention: cSMT (defined as a manual therapy technique
that uses a high velocity low amplitude thrust applied at a spinal
motion segment ) [12].
Comparison: Not relevant.
Outcomes: Cervical arterial dissections (defined as longitudi-
nal disruptions in an artery’s wall
19
in the common carotid,
internal carotid, vertebral, or vertebrobasilar) or stroke (defined as
a sudden loss of brain function caused by a blockage or rupture of
a blood vessel to the brain, with neurological symptoms that vary
with the extent and severity of the damage to the brain) [13].
Language: Articles in either English or French were consid-
ered for inclusion.
Study Selection
Titles and abstracts of records obtained from the search were
screened by two independent reviewers (SW and MW). The full
texts of potentially relevant studies were then screened indepen-
dently by the same two reviewers using the inclusion criteria
described below. Where reviewers disagreed, consensus was
resolved by discussion.
Assessment of Reporting Quality
To evaluate the quality of cases that reported an association
between cSMT and CAD, 21 factors were derived from Bradford-
Hill criteria (Table 2) which are often employed to explore causal
associations. Of these, 10 have the potential to be reported in case
reports (specifically, 1) time-to-onset of symptoms, 2) the vessel that
was injured, 3) the anatomic location of the injury, 4) report of co-
morbidities, 5) presence of head and/or neck pain, 6) type of
cSMT performed, 7) location cSMT application, 8) profession of
cSMT provider, 9) previous number of cSMTs, and 10) patient’s
demographics (i.e. age, gender, and health status)). The presence
or absence of each of these 10 factors within the screened studies
was then determined through full manuscript review performed by
two reviewers. In addition to the 10 factors derived from Hill’s
criteria, an 11
th
factor regarding the stroke type was collected and
tabulated. Disagreements regarding the presence or absence of any
of the 11 factors were resolved by consensus. The reporting
frequency of each factor was then calculated.
Analysis
We could not identify any standard guidance regarding the
conduct of meta-analysis from case reports and case studies and
therefore data are summarized in text. All relevant information for
the CAD and stroke cases were collected, tabulated and expressed
as a percentage.
Results
The flow of studies through this review can be found in the
Preferred Reporting Item for Systematic Reviews and Meta-
Analyses (PRISMA) diagram [14] contained in Figure 1. The
electronic search strategy identified 427 papers of which 131 were
duplicates. Screening based on title and abstract excluded another
242 papers. Of the 54 remaining papers, 11 were excluded for the
following reasons: four reports were duplicate forms of publication
[3,15–17], two did not contain cSMT [18,19], four were reviews
rather than primary data [5,20–22] and one was a cadaveric study
[23].
CAD Diagnosis
The diagnosis of CAD was reported in all articles included in
this manuscript. Approximately 70% of the cases reported
described dissection of the vertebral artery and carotid artery. In
the reported cases, a subset of 852 cases confirmed the diagnosis
using either angiography (34%), magnetic resonance imaging (with
or without angiography) (34%), and computed tomography (9%).
The remaining 23% of the cases were confirmed using other
methods such as Doppler ultrasonography and duplex sonogra-
phy. In all imaging studies, criteria such as the appearance of
stenotic vessels, flow abnormalities, or the presence of an intimal
flap were used to confirm the CAD diagnosis, The largest study
performed by Rothwell et al did not provide any information
regarding how the diagnosis of CAD was made [9].
Stroke Type
Of the 901 cases of CAD associated with cSMT, 707 (85%)
cases reported stroke type; however, the anatomical location of the
infarct was only reported in 32 out of the 706 ischemic infarcts.
Strokes reported post-cSMT were all ischemic, with one hemor-
rhagic transformation in the parietal-occipital region [24]. Table 3
summarizes the stroke-type reported in this cohort of studies.
There were 56 cases described by the authors as having vascular
compromise without any infarcts associated with their CAD.
Table 1. Keyword search and Boolean Operators*.
Keyword
1 Vertebral artery dissection
2 Internal carotid dissection
3 Cervical artery dissection
4 Chiropractic
5 Manual therapy
6 Spinal manipulation
7 Stroke
813OR
9 8 AND 4
10 8 and 5
11 4–6 OR
12 11 AND 7
*Search was limited to human subject only, year (January 2001 to January
2011).
doi:10.1371/journal.pone.0059170.t001
CAD following Cervical SMT: A Systematic Review
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Additionally, there were 3 cases identified where the CAD caused
neuro-vascular compromise leading to Horner’s syndrome.
Quality of Reporting
Of the 43 articles that met inclusion criteria for this study, there
were 24 case reports [24–47], 14 case series [6–8,48–58], two
surveys [59,60], two cohort studies [9,61], and one commentary
[62]. Of these included studies, some contained a mix of cases that
were not always associated with cSMT. Of the 1344 cases of CAD
described in the included studies, 901 were reported as preceded
by cSMT. The frequency of each of the criteria factors reported in
these 901 cases are summarized in Table 4. No single case report
described all factors thought to be meaningful to the further
understanding of cSMT and CAD. Of the reported factors, time-
to-onset of symptoms was reported most frequently (95% of cases)
with the next-most frequently reported factor being vessel injury
location at 57%. While 57% may be thought of as adequate, this
information may not be useful as few, if any, cases reported the
anatomic location of damage within the vessel itself. Furthermore,
many of the larger reported case series were composed of a
heterogeneous population making extraction of specific vessel and
injury location for only the cSMT cases difficult. For example, one
large study (126 patients) had 20 patients that had cSMT prior to
reporting to the hospital with CAD. In this same study, the authors
report which vessels were injured for the entire patient population
(126 patients) but fail to identify the injury location in the cSMT-
patient population specifically [7].
cSMT-specific Factor Reporting
Papers were reviewed for an 11
th
criteria regarding cSMT-
specific factors (e.g. location of therapy application, type of cSMT).
Only one paper described the cSMT procedure itself or the
anatomic location of cSMT application [9] while only 9%
reported on the frequency of pre-incident cSMT application (i.e.
patient history of previous cSMTs). Figure 2 summarizes the
distribution of factors in the included articles.
Discussion
This study assessed the quality of investigations that reported
cSMT associated with CAD by determining the frequency with
which specific quality factors were described. Because it is
Table 2. Data Extraction Elements related to Bradford-Hill causality criteria.
Hill’s Causality Criteria Description Related data extraction elements
Temporality The temporal relation between the presence of a
factor and the occurrence of some disease.
Time-to-onset of symptoms
Strength of Association The magnitude of the relative risk associated between
developing an adverse outcome with exposure to an agent.
Number of CAD associated with cSMT**
Number of Exposed to cSMT**
Number of CADs occurring without cSMT**
Number of Non-exposed**
Consistency The extent to which the findings are similar
across the body of evidence .
Number cSMT related CADs**
Number of non-cSMT related CADs**
Biologic Gradient The observed relation between a factor and a disease
must be related by the amount of exposure of that factor to
the disease.
Previous number of cSMTs
Force of cSMT**
Biological Plausibility/
Coherence*
The knowledge of a biological mechanism of action for the
creation of a disease by a known factor.
Vessel that was injured
Anatomic location of the injury
Anatomical variations
Presence of head and/or neck pain
Report of co-morbidities
Type of cSMT performed
Location of cSMT application
Profession of the cSMT provide r
Specificity The extent to which a single, well-characterized factor can
be shown to be present for each case of a disease.
Examination of the reported data features that occur
specifically with cSMT related CADs. **
Experiment Use of basic science inquiry to test hypotheses regarding
the cause of a disease based on population data information.
Prospective studies **
Basic science data (i.e. animal models of CAD, measurement of
forces during cSMt etc.)**
Analogy Assignment of a causal interpretation based on the
similarity of an association with another association.
Examination of motor vehicle accident or trivial trauma
incidence of CADs and compare with cSMT incidence of
CADs.**
*The criterion of coherence is typically considered analogous to biological plausibility criterion and usually combined with this criterion
71
.
**Features that cannot be determined through a systematic review of case studies, case series, or cohort studies.
doi:10.1371/journal.pone.0059170.t002
CAD following Cervical SMT: A Systematic Review
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recommended that case reports should be included in systematic
reviews of relatively rare harms, the quality of these reports is of
critical importance in knowledge synthesis. Overall, the quality of
case reports examined in this study was low in that they
infrequently contained more than 5 of the 11 relevant factors.
Certainly, previous papers have also identified limitations of
case reports within the cSMT/CAD literature. A previous review
provided limited data regarding subject demographics, time-to-
onset of symptoms, and the profession of the cSMT provider [63].
Based on this, Kawchuk et al. showed that two of the largest case-
series involving cSMT/CAD to date did not report CAD location.
Although this information was unreported, the information was
available. As a result, a secondary analysis was performed that
demonstrated that in cases where CAD was reported to follow
cSMT, lesions in the vertebral arteries were not distributed
randomly [64]. This study demonstrates that by providing
clinically relevant factors within case reports, further synthesis
toward understanding the relation between cSMT and CAD is
possible.
In studying the association between cSMT and CAD, it is
important to understand the events preceding the application of
cSMT and the onset of CAD. Unfortunately, the results from this
study demonstrate a general deficiency in reporting events
preceding cSMT or CAD other than that the patient presented
to the emergency clinic following cSMT. Clearly, case reports
discussing the development of a stroke should endevour to include
an etiological work-up so that an alternative cause of the patient’s
presentation might also be elucidated. For example, spinal
manipulation is a therapeutic modality that is used to treat head
and neck pain [65]. The reasons for the presentation of head and
neck pain may be minor trauma (i.e. motor vehicle accident). If a
CAD then occurs following cSMT, it becomes difficult, if not
impossible, to identify which event, if any, were associated with the
injury. This paper clearly demonstrates that there is a critical need
to report all events surrounding CAD, not just the event
immediately preceding the injury.
Identifying the stroke type when reporting cSMT associated
with CADs would be useful for those practitioners who frequently
examine patients presenting to the emergency room (or clinic) with
stroke-like symptoms following a therapeutic intervention. Under-
standing of the typical stroke presentation might help with rapid
identification of injury location and assist in the determination of a
management protocol. Our study demonstrates that while stroke
type was reported often, the anatomical location of the stroke was
not. Given that stroke symptoms are specific to the area affected
by the lesion, further understanding of the management of patients
with strokes thought to be associated with cSMT might occur with
increased reporting of injury location rather than simply stating
the type of stroke.
The lack of reporting regarding cSMT-specific factors was
similar to the under-reporting of other factors. This is an
important omission as there is an inherent variability of cSMT
techniques used by manual therapists. While some investigators
have examined the mechanical forces associated with instrument-
assisted spinal manipulation [66], there are few studies that have
examined the differences between the various types of cSMT [67].
Clearly, understanding the distribution of cSMT and the type of
cSMT provided would generate important data regarding the
safety of various cSMT procedures.
Our study has demonstrated that there are deficiencies in
reporting key factors associated with CAD and cSMT. While the
temporality and location of the injury were reported consistently,
additional efforts are needed to improve harms reporting so that
clinicians are provided with accurate information about various
therapies and their potential sequelae. One approach to improved
reporting has been suggested by the EQUATOR (Enhancing the
Quality and Transparency of health Research) network comprised
of researchers working towards improved quality of the published
literature. The network hosts an up-to-date library of reporting
guidelines for health research on their website (www.equator-
network.org). Currently, at least two sets of guidelines have been
identified which if used, may improve the quality of case report
literature [68,69]. In addition examples of standardized reporting
tools used to evaluate the cause of adverse events exist such as the
Consolidated Standard of Reporting Trials (CONSORT) State-
Figure 1. PRISMA Flow chart.
doi:10.1371/journal.pone.0059170.g001
Table 3. Type of stroke associated with cSMT (Total number
of cases = 707).
Stroke Type
Number of
Cases
Infarcts 706
Ischemia (location not discussed) 674
Brainstem 9
Cerebellar 8
Medullary 8
Occipital 1
Parietal 1
Pontine 1
Subcortical 1
Temporal occipital 1
Thalamic 1
Multiple Infarcts 1
Hemorrhagic Infarcts 1
Parietal-occipital 1
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ment for reporting adverse events in clinical trials, [70] and the
Naranjo Causality Scale for reporting adverse reactions to
pharmaceuticals. [71] The use of these standardized reporting
tools for monitoring the safety of treatments within clinical trials
demonstrates that through effective use of clinical information, the
causes of adverse events might be identified early so as to prevent
further incidents. Currently, there is no standardized reporting
tool for examining adverse events associated with cSMT.
Therefore, in the interest of further understanding CAD in
relation to cSMT, a standardized reporting tool should be
developed. Implementation of consistent reporting of all data
features for all CADs may provide clinicians and researchers with
more, and better, information to 1) understand which patients are
at risk of developing a post-cSMT CAD and 2) possibly decrease
the overall incidence of post-cSMT CAD events.
In addition to a standardized tool for reporting cases where
adverse events are associated with cSMT, it is important to
standardize how the diagnosis of CAD is achieved. The diagnosis
of CAD is exceedingly difficult and has to be performed with
sufficient quality to ensure that the patient had a CAD rather than
some other cause of arterial occlusion, stenosis, or hypoplasia.
Failure to diagnosis a CAD accurately places a limitation in the
interpretation of the data found in the case report. The diagnosis
of CAD should be made from the visualization of a transmural
hematoma or a pseudoaneurysm with long tapering stenosis and/
or an intimal flap or double lumen [72]. Further standardization of
the diagnostic criteria for CADs is important for improving the
quality of CAD case reports.
A potential limitation of this study was the lack of an existing
tool to measure case report quality in this topic area. Given this
void, and the recommendations of the Cochrane Collaboration to
include case reports in systematic reviews designed to investigate
infrequent harms, we developed a list of 11 factors to describe case
report quality based on well-established criteria used to explore the
relation between cause and effect [73]. While this approach
provides one way to measure the quality of case report material, it
may not be the only relevant way to achieve this goal. As such,
future measures of case report quality may arrive at a different
conclusion; however, the observed deficiencies of the existing case
report literature remain. By collecting and collating information
from multiple reports, a better understanding about the association
of cSMT, CADs and stroke will be possible.
Another potential limitation of this study is publication bias.
Specifically, not every case of cSMT associated with CAD is
published in the scientific literature. In fact, previous papers
[16,64] present data from medico-legal proceedings that were not
published in the academic literature. This bias suggests that there
is under-reporting of the cases of CAD associated with cSMT, and
suggests that a more complete examination of data should include
examination of those cases in medico-legal proceedings.
Conclusions
This paper examined the quality of literature describing an
association between cSMT and CAD. Case reports represented
the majority of this literature. Since these reports may contribute
to further understanding CADs as they relate to manual therapy, it
is important that they are of the highest quality. This study has
Table 4. Reported variables where cSMT was reported to have occurred prior to the onset of CAD. (n = 901).
Hill’s Criteria Reported Variables Number of Reported Cases (%)
Temporality Time-to-onset of symptoms 840 (93%)
Biologic Gradient Previous number of cSMTs 78 (9%)
Biological Plausibility Type of cSMT performed 69 (8%)
Rotary Application 30 (3%)
Other types (i.e. instrument) 39 (4%)
Location of cSMT application 1 (,1%)
Biological Plausibility Vessel that was injured 638 (71%)
Vertebrobasilar injuries 633
Carotid artery injuries 6
Anatomic location of the injury 57 (6%)
Anatomical variations 1 (,1%)
Presence of head and/or neck pain 93 (10%)
Report of co-morbidities 83 (9%)
History of smoking 17
Hypertension 12
Fibromuscular dysplasia and other chronic diseases (i.e. diabetes mellitus) 11
Use of birth control pills 15
History of migraines 26
History of recent infection 2
Profession of the cSMT Provider 896 (99%)
doi:10.1371/journal.pone.0059170.t004
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demonstrated that the literature infrequently reports useful data
toward understanding the association between cSMT, CADs and
stroke. As a result, the value of these reports toward informing our
understanding of the relation between cSMT and CAD is
minimal. We suggest that through the systematic collection of
data features presented in this paper, a clearer clinical picture of
the association between cSMT and CAD would be possible. This
study lays the groundwork for developing a universal reporting
tool for adverse events related to cSMT.
Supporting Information
PRISMA Checklist S1
(PDF)
Acknowledgments
The authors wish to acknowledge Sherry Mahanna (Texas Chiropractic
College) who assisted in the literature search and article retrieval and
Larissa Shamseer who provided editorial comments to several drafts as well
as methodological support for the review.
Figure 2. Overall number of quality factors contained in the 43 reviewed articles.
doi:10.1371/journal.pone.0059170.g002
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Author Contributions
Conceived and designed the experiments: SW SV GK. Performed the
exper iments: SW MW. Analyzed the data: SW MW. Contributed
reagents/materials/analysis tools: SV GK. Wrote the paper: SW MW
SV GK.
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