Headache ISSN 0017-8748

© 2009 the Authors doi: 10.1111/j.1526-4610.2009.01550.x

Journal compilation © 2009 American Headache Society Published by Wiley Periodicals, Inc.

Research Submission
Lack of Efficacy of Manual Therapy in Children and
Adolescents With Suspected Cervicogenic Headache:
Results of a Prospective, Randomized, Placebo-Controlled, and
Blinded Trial head_1550 224..230

Peter Borusiak, MD; Heiner Biedermann, MD; Stephanie Boßerhoff, MD; Joachim Opp, MD

Objective.—Clinical trials concerning cervical spine manipulation and mobilization in children and adolescents with
cervicogenic headache are lacking.
Methods.—We performed a multicenter, prospective, randomized, placebo-controlled, and blinded trial in 52 children and
adolescents (21 boys, 31 girls) aged 7-15. After prospective baseline documentation for 2 months patients were either assigned
to placebo or true manipulation with another 2-month follow-up. Main outcome measures were defined as: percentage of days
with headache, total duration of headache, days with school absence due to headache, consume of analgesics, intensity of
headache.
Results.—We did not find a significant difference comparing the groups with placebo and true manipulation with respect
to the defined main outcome measures.
Conclusions.—We were not able to show an efficacy of cervical spine manipulation in 52 children and adolescents.
Key words: manual therapy, migraine, tension-type headache, cervicogenic headache, spinal manipulation therapy
Abbreviations: GNP German Neuropediatric Society, IHS International Headache Society, SMT spinal manipulative therapy,
TENS transcutaneous electrical nerve stimulation, VAS/NAS visual/numerous analog scale

(Headache 2010;50:224-230)

Headache is very widespread and ranks as one of
the most common disease of childhood with up to
51% of children aged 7 years old and 57-82% of
15-year-olds reporting recurrent headaches.1,2 Pre-
ventive options include pharmacological treatment
From Sozialpädiatrisches Zentrum, HELIOS Klinikum, Wup-
pertal, Germany (P. Borusiak); Praxis für Manualtherapie,
Cologne, Germany (H. Biedermann); Sozialpädiatrisches
Zentrum, Marien-Hospital, Wesel, Germany (S. Boßerhoff);
Sozialpädiatrisches Zentrum, Evangelisches Krankenhaus,
Oberhausen, Germany (J. Opp).
Address all correspondence to P. Borusiak, Zentrum für
Kinder- und Jugendmedizin, Helios Klinikum Wuppertal,
Heusnerstr. 40, D-42283 Wuppertal, Germany.
Accepted for publication August 31, 2009.
even if there is a disappointing lack of evidence from
controlled, randomized, and masked trials for a clini-
cal problem so prevalent in children and adolescents.3
Craniocervical blockages have been claimed to cause
headache of different type, severity, and frequency.4
One study in adults showed that spinal manipulative
therapy (SMT) might be an effective treatment for
tension-type headache.5 Nevertheless, the significance
of this therapy and its side effects are under debate.6
This is at least partially due to different approaches to
SMT as well as limited, poorly designed studies.7
Conflict of Interest: Peter Borusiak, Stephanie Bosserhof, and
Joachim Opp have no conflict of interest to disclose. Heiner
Biedermann is a manual therapist.

224
Headache
Considering adverse events associated with pediatric
spinal manipulation neither causation nor incidence
rates are known due lack of prospective population-
based active surveillance studies. A recent review on
this topic cites estimations of vertebrobasilar acci-
dents in adults ranging from 1 in 20,000 patients to 1
per 1 million cervical manipulations.8 Manual therapy
is a popular form of treatment in Germany and the
impact of craniocervical blockages for recurrent
headache is recognized by several medical associa-
tions in Germany.9,10 Yet, this therapeutic approach is
under debate and controlled studies in children are
lacking. A report of the German Neuropediatric
Society (GNP) states that SMT is found to be
effective in single patients and calls for controlled
studies.11
Cervicogenic headache is listed in the Interna-
tional Classification of Headache Disorders with a
clear reference to the lack of conceptual clarity.12
Clinical signs such as neck pain or focal neck tender-
ness may be features of cervicogenic headache, but
they do not define the relationship between the dis-
order and the source of the headache. One criterion
for cervicogenic headache is that headache resolves
or greatly improves after effective treatment. To our
knowledge ours is the first study to investigate the
efficacy of SMT in children and adolescent with recur-
rent headache.
METHODS
The study was designed according to the
guidelines for controlled trials of the International
Headache Society (IHS).13,14 Slight modifications
were necessary as the guidelines are at least partially
specific for different types of headache, adults, and
drug therapy.13,14 Migraine and tension-type headache
can occur in the same patient and identification of
cervicogenic origin might be difficult in some patients
with only retrospective assignment after improve-
ment or resolution of the headache after relief from
the craniocervical disorder. Thus we included all
patients with headache regardless of apparent type
and planned a later differentiation of subgroups. The
study was approved by the local ethics committee of
the University of Witten-Herdecke and all patients
225
and their parents gave verbal and written informed
consent prior to participation.
Participants.—All children and adolescents who
were seen at the regular headache outpatient clinic at
one of the neuropediatric departments in Wuppertal,
Oberhausen, and Wesel with headaches for more than
6 months at least once a week and who were between
7 and 15 years of age, were candidates for inclusion in
the study. They were not admitted to the study if any
of the following criteria were present: (1) secondary
headache other than of cervicogenic origin; (2) previ-
ous manual therapy; (3) other parallel therapies like
constant preventive analgesic treatment, transcut-
aneous electrical nerve stimulation (TENS), or psy-
chological interventions; or (4) unwillingness to
participate or return for follow-up. The participating
neuropediatric departments are outpatient clinics
serving as tertiary referral centers. Local pediatricians
were informed about the study.
Interventions.—At the first visit (V1) patients with
recurrent headache underwent routine diagnostic
procedures in the outpatient clinic as recommended
by the GNP and different therapeutic options accord-
ing to the guidelines were discussed with patients and
their parents. We also offered a free participation in
the SMT-trial and provided an additional handout. A
diary and a visual analog scale with possibility to
convert into a 10-point numerous analog scale (VAS/
NAS) were supplied for the first prospective
documentation period (DP1).15 If patients and their
parents gave informed consent, at the next visit (V2)
after 2-month prospective documentation, and were
matching the inclusion criteria, they were randomized
by a computerized random-number generator to
receive either placebo or true SMT. Blocking with
blocks of 8 patients was used to ensure close balance
of the numbers in each group at any time during the
trial. The assignments were sealed in sequentially
numbered identical, opaque envelopes according to
the allocation sequence and opened by the manual
therapist (H.B.) immediately before the intervention.
Patients, their parents, and the neuropediatricians
were blinded for the result of randomization.
Both interventions – placebo and true SMT –
were performed in the same position after an a.p.
x-ray picture of the suboccipital region and cervical
226
spine and a careful examination of the participant by
the same physician (H.B.). Patients were lying on the
side and a cervical high-velocity, low-amplitude
lateral directed manipulation without rotation or
extension was performed.11 Forces of this interven-
tion are known and vary from 50 Nm in newborns and
infants to 350 Nm in adults.16 The sham treatment of
placebo group consisted of a light touch of specific
spinal segments so that the placebo treatment was
identical to the active treatment except for the low-
amplitude, high-velocity thrust, given the impression
of a cervical manipulation that however was not
directed to correct the assumed cervical blockage.
After the procedure patients were asked whether
they think they received the real treatment or
placebo. Also a systematic evaluation of side effects
and adverse events was performed immediately after
the cervical manipulation and after the following
2-month follow-up period. Adverse events were clas-
sified according to proposed criteria8 using the follow-
ing categories: severe (indicating hospitalization,
permanent disability, mortality), moderate (transient
disability, involving seeking medical care but not
hospitalization), minor (self-limited, did not require
additional medical care), and delayed diagnosis or
treatment (moderate to severe adverse event not
directly related to the spinal manipulation but as a
result of delayed diagnosis or treatment of a medical
condition). At the third visit (V3) after the 2-month
documentation period following the intervention
(DP2) all patients were offered an open and true
intervention of SMT.
Objectives and Outcomes.—In the current study
we tested the hypothesis that SMT in children and
adolescents with suspected cervicogenic headache
would influence the complaints. Outcome parameters
were defined with respect to relevance of daily life
with a change of at least 40% comparing DP1 and
DP2 considering: (1) percentage of days with head-
ache; (2) total duration of headache; (3) percentage of
days with missing school lessons due to headache; (4)
percentage of days with necessity of analgesic medi-
cation; and (5) intensity of headache. For percentage
of days with missing school lessons due to headache
data were corrected for actual school days (eg, holi-
days excluded). Subgroup analyses were planned for
February 2010
differences considering gender, different types of
headache (tension type, cervicogenic, and migraine),
and severity of complaints (high vs low frequency, and
high vs low intensity).
Sample Size.—The estimated placebo effect in
migraine prophylaxis is usually considered in the
range 20-40% and around 30% in tension-type head-
ache.13,14 According to previous experience in treating
children and adolescents with headache we believed
that the responder rate in the SMT group would be at
least 55%. Based on a power of 95% to detect a
significant difference (P = .05, two-sided), 99 patients
were required for each study group. To compensate
for non-evaluable patients, we planned to enroll 110
patients per group. We planned an interim analysis in
order to review the results of the study every 50
patients to enable the study to be stopped early if, as
indeed occurred, a clear result emerged or our previ-
ous assumptions proved to be wrong.
Statistical Methods.—Data analysis was carried out
according to a pre-established analysis plan. Most
data were calculated and given as percentages thus
allowing for correction of individually different
length of eg, DP1 and DP2. Proportions were com-
pared by using chi-square tests with continuity cor-
rection. Additionally we performed an analysis of
changes from baseline to follow-up period using
paired t-test. Two-sided significance tests were used
throughout.
RESULTS
Age-eligible participants were recruited from
September 2002 to October 2007. The trial was
stopped owing to results of interim analysis of the
data. Not only the responder rate in the SMT group
was different from our initial assumption. In this
analysis we found a much higher variation of docu-
mented complaints than previously assumed. Because
of the diversity of frequency and intensity of head-
ache a new power analysis was performed on the base
of the existing data. Excluding the top and undermost
10% we calculated another 600 patients in each group
necessary to complete the study.
A total of 56 patients started the study; there
were no differences according to starting conditions
and variances of tested baseline parameters between
Headache 227

Assessed for eligibility

(n= 188)

Excluded (n=132)

Not meeting inclusion

criteria (n=96)

Refused to participate
(n=36)

Randomized (n=56)

Allocated for SMT Allocated for Placebo

(n= 28, all received (n= 28, all received
allocated intervention) allocated intervention)

4 lost to follow-up 0 lost to follow-up

24 analyzed 28 analyzed
1. n=24 1. n=28
2. n=18 2. n=19
3. n=24 3. n=27
4. n=24 4. n=27
5. n=20 5. n=19

Figure.—Flow diagram. (Numbers from 1 to 5 in the last 2 squares apply to patients with sufficient data with respect to outcome
parameters: 1 = percentage of days with headache, 2 = total duration of headache, 3 = percentage of days with missing school lessons
due to headache, 4 = percentage of days with necessity of analgesic medication, and 5 = intensity of headache).

the placebo (n = 28) and the SMT group (n = 28).
Finally 52 patients (21 boys, 31 girls; age 11.6 ⫾ 2.3
years) were included in the analysis (Fig.). The dura-
tion of the prospective baseline documentation from
first visit to intervention was 56.4 ⫾ 13.0 days and
59.8 ⫾ 16.7 days for the follow-up period. Comparing
baseline and follow-up the frequency of days with
headache was reduced both in the SMT and the
placebo group; however, the differences between
both groups were not significant. Considering the
other outcome measures, we did not find significant
changes (Table). Due to the reduced sample size we
abstained from further planned subgroup analyses.
As none of the participants had previous experience
with SMT they were unable to distinguish between
placebo and sham treatment. In the placebo group
13/28 patients guessed they received sham treatment,
10/28 reckoned the treatment as true intervention,
and 5/28 were unable to tell. Treatment was classified
as placebo in 11/28, as true SMT in 11/28 in the SMT
therapy group with 6 children unable to tell. No
severe or moderate side effects were noticed and the
same holds true for the category of delayed diagnosis
or treatment. Patients and parents did only report
minor adverse events without significant or clinically
relevant differences comparing the patients with
SMT and sham treatment with hot skin and dizziness
being reported most often in 15 (treatment group: 6;
placebo group: 9) and 11 patients (treatment group: 7;
placebo group: 4), respectively. All patients recovered
spontaneously with no reported sequelae. Length of
recovery period was from few seconds to 15 minutes
228
Table.—Results
Baseline (DP1)
Percentage of days with headache (in %)
Treatment group 40.4 ⫾ 28.3
Sham group 41.2 ⫾ 28.5
Total duration of headache (in h)
Treatment group 149.6 ⫾ 195.7
Sham group 113.8 ⫾ 115.1
Percentage of days with missing school lessons due to headache (in %)
Treatment group 3.9 ⫾ 6.0
Sham group 3.3 ⫾ 5.4
Percentage of days with necessity of analgesic medication (in %)
Treatment group 11.6 ⫾ 16.9
Sham group 8.5 ⫾ 9.6
Intensity of headache (VAS/NAS)
Treatment group 4.3 ⫾ 1.6
Sham group 4.9 ⫾ 1.8
in most adverse events but a transitory increase in
headache intensity and frequency being reported for
up to 4 days (8 patients in the treatment group, 6 in
the placebo group).
DISCUSSION
Despite the frequency and impact of recurrent
headache on children’s and adolescents’ lives there
are hardly any studies evaluating pharmacological
and non-drug treatment options. Many children and
their parents are reluctant to use medicine especially
on a regular basis. Chiropractic medicine is one of
the most common complementary medicine practice
used by children due to a variety of reasons.17 A theo-
retical basis for the effect of SMT in recurrent head-
ache was demonstrated by Bogduk showing that head
pain similar to that of tension-type headache might be
caused by stimulating structures that are innervated
by nerval roots from C1 to C3.18 Previous data in
adults on efficacy of SMT are diverging. As some
authors found positive effects and state that SMT
appears to have an effect similar to frequently used
first-line prophylactic medications others failed to
demonstrate effects in randomized controlled tri-
als.5,6,19 Improvement of headache frequency after
intervention is consistent with data from the litera-
ture. As the study of SMT in adults with episodic
tension-type headache in adults19 we failed to demon-
February 2010
Follow-up (DP2) Paired t-test
30.7 ⫾ 32.9 P = .009
31.8 ⫾ 28.3 P = .027
142.1 ⫾ 211.9 P = .31
107.2 ⫾ 121.1 P = .13
5.5 ⫾ 12.5 P = .42
2.7 ⫾ 3.7 P = .34
9.8 ⫾ 21.2 P = .46
9.5 ⫾ 12.7 P = .37
4.0 ⫾ 1.8 P = .42
5.0 ⫾ 1.8 P = .42
strate superiority of true SMT over sham treatment in
a first placebo-controlled, prospective, blinded, and
randomized trial in children and adolescents. We did
not find a significant difference in any of the 5 defined
relevant parameters. However, several restrictions
apply and potential bias must be taken into consider-
ation. First of all our study was initially designed for
220 patients and was stopped due to interim analysis
after inclusion of only 52 patients. Potential bias
might be due to the character of the participating
neuropediatric departments as tertiary referral
centers. Local pediatricians referring the patients as
well might have selected patients. As the debate
about SMT in Germany is very fierce bias might
extent in both directions. Either mostly children who
are considered responders due to clinical impression
or patients previously reckoned as probable non-
responders might have been referred. Compared with
a study in adults where SMT showed a comparable
efficacy as amitriptyline5 our patients documented a
higher intensity of headache throughout the study.
Headache intensity in the amitriptyline study varied
from 5.0 to 5.6 on a 0-20 scale compared with 4.3 to
4.9 on a 0-10 scale in our patients. On speculative base
patients with lower intensity of pain might be more
likely to profit.
Another potential bias might be due to our rela-
tively strict inclusion criteria with more than 130
Headache
patients excluded. This exclusion was mainly due to
the frequency of headache with many children not
having complaints at least once a week. We cannot
answer the question whether a gender-related differ-
ence or a discrepancy between children with tension-
type headache or migraine exists. In addition the
possibility of cervicogenic headache must be consid-
ered in those patients who showed improvement
after SMT as according to the guidelines of the IHS
abolition of headache following intervention is a
diagnostic criterion for this subgroup.
Another factor influencing the results might be
an observational bias: in children with lower intensity
and frequency of headache a medical trial might focus
attention on the discomfort whereas in the group with
higher complaints any intervention might at least
temporarily relieve the pain. Furthermore the debate
on the appropriate kind of manipulative intervention
in SMT is still going on.
In our trial, the number of participants was rela-
tively small and the question of a possible type 2 error
(ie, overlooking a real difference) is an issue. It is
possible that a larger trial might have identified an
effect in one or more of the main outcome measures.
We suggest that further trials should focus on either
children with migraine, tension-type headache, or cer-
vicogenic headache although in practice, different
types can be difficult to differentiate and might often
occur together. Another suggestion is that inclusion
criteria should be restricted to better allow the possi-
bility of seeing a change by using more typical rather
than very mild or severe cases as in the aforemen-
tioned study.19
Acknowledgments: This study was supported by the
Wagener-Stiftung (Wagener Foundation). The authors
would especially like to acknowledge Sigrid Müller for
statistical programming support.
STATEMENT OF AUTHORSHIP
Category 1
(a) Conception and Design
Peter Borusiak; Heiner Biedermann
(b) Acquisition of Data
Peter Borusiak; Heiner Biedermann; Joachim
Opp; Stephanie Boßerhoff
229
(c) Analysis and Interpretation of Data
Peter Borusiak; Heiner Biedermann; Joachim
Opp; Stephanie Boßerhoff; Sigrid Müller
Category 2
(a) Drafting the Manuscript
Peter Borusiak; Heiner Biedermann
(b) Revising It for Intellectual Content
Peter Borusiak; Heiner Biedermann; Joachim
Opp; Stephanie Boßerhoff
Category 3
(a) Final Approval of the Completed Manuscript
Peter Borusiak; Heiner Biedermann; Joachim
Opp; Stephanie Boßerhoff
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