Prevalence of Atlanto-Occipital and Atlanto-Axial Instability in Adults with Down Syndrome.

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Prevalence of Atlanto-Occipital and Atlantoaxial Instability in Adults with
Down Syndrome
Marcelo El-Khouri
1
, Marcelo Alves Moura
˜o
1
, Andrea Tobo
1
, Linamara Rizzo Battistella
1,2
,
Carlos Fernando Pereira Herrero
3
, Marcelo Riberto
3
INTRODUCTION
Down syndrome (DS) is the most common
and well known of all malformation syn-
dromes in humans. It occurs in approxi-
mately 1 in every 700 to 900 live births, a
number thatincreases directlywith maternal
age, reaching a proportion <1:1000 among
pregnant women older than 40 years (24).
The clinical picture typically consists of
characteristic facial features, hypotonia,
mental retardation, and several malforma-
tions involving the circulatory and digestive
systems.
Multiple body deformities can be
observed in these individuals. Among the
musculoskeletal disorders are cervical spine
problems, mainly instabilities between the
occiput and the first cervical vertebra, or
involving the first and the second cervical
vertebrae (10). Relevance of these findings
lies in their unstable nature and potential to
cause severely disabling or fatal injuries due
to their proximity to nervous structures
responsible for breathing control (17).These
musculoskeletal disorders have been stud-
ied more often among children because the
American Academy of Pediatrics suggests
restrictions for the practice of exercises by
younger subjects with this syndrome and
cervical instability, but little is known about
this issue in adults or about the progression
of such disorders (25).
The increased life expectancy of these
individuals and the growing stimulus to the
practice of adapted sports as a strategy for
psychomotor development and prevention
of cardiovascular diseases has resulted in a
deeper search for medical evaluations for
sports activities. Thus, for adult Brazilians
with DS, it is relevant to systematically
evaluate the prevalence of these musculo-
skeletal conditions and correlate them with
the clinical context and sports activities.
The aim of this study was to define
the prevalence of atlanto-occipital axial
instability in adults with DS, with or without
symptoms, and to define any associated
factors. We also compared techniques used
in the radiological identification of high
cervical instability.
METHODS
This was a cross-sectional study. From
2002 to 2007, we monitored subjects over
18 years of age with DS at the Division of
Rehabilitation Medicine of a general hos-
pital associated with the School of Medi-
cine at the University of São Paulo, Brazil.
Aside from training for daily living activ-
ities and development of cognitive and
social skills, like many other rehabilitation
centers, one of the objectives of this fa-
cility is to introduce and develop sports
abilities for people with disabilities. For
adults with DS in particular, this work was
focused on sports and socialization. All of
the individuals with DS who were included
in the modalities of adapted exercises
-OBJECTIVE: This study sought to evaluate the presence of atlanto-occipital
and atlantoaxial instabilities as well as their clinical significance in patients
with Down syndrome.
-METHODS: The present study retrospectively evaluated 80 adults with Down
syndrome for the presence of atlanto-occipital and atlantoaxial instability in
lateral craniocervical radiographic images. Atlanto-occipital instability was
defined by the Rules of 12 or Harris measurements, using the values of the basion-
dens interval or the basion-axial interval. Atlantoaxial instability was radiologi-
cally identified by the space between the anterior border of the odontoid apophysis
and the posterior border of the atlas arch, as well as by the Wiesel-Rothman line.
-RESULTS: Eighty patients were assessed; 14 (17.5%) presented with atlanto-
occipital instability and 9 (11.2%) with atlantoaxial instability. Only 3 patients
(3.8%) had specific symptoms for cervical instability. There was no statistical
correlation with patient age or gender.
-CONCLUSIONS: High cervical instability in patients with Down syndrome can
also be observed among adults, and there is a low correlation between the
radiological findings and symptoms. These findings emphasize the importance of
periodic follow-up on these patients, particularly when sports activities are
considered.
Key words
-Adult
-Atlantoaxial instability
-Atlanto-occipital instability
-Down syndrome
-Prevalence
Abbreviations and Acronyms
AAI: Atlantoaxial instability
AOI: Atlanto-occipital instability
BAI: Basion-axial interval
BDI: Basion-dens interval
DS: Down syndrome
From the
1
Institute of Physical Medicine and
Rehabilitation of Hospital das Clínicas of the
University of São Paulo;
2
School of Medicine in São Paulo,
University of São Paulo; and
3
Ribeirão Preto Medical School,
University of São Paulo, São Paulo, Brazil
To whom correspondence should be addressed:
Marcelo Riberto, M.D., Ph.D.
[E-mail: mriberto@usp.br]
Citation: World Neurosurg. (2014) 82, 1/2:215-218.
http://dx.doi.org/10.1016/j.wneu.2014.02.006
Journal homepage: www.WORLDNEUROSURGERY.org
Available online: www.sciencedirect.com
1878-8750/$ - see front matter ª2014 Elsevier Inc.
All rights reserved.
WORLD NEUROSURGERY 82 [1/2]: 215-218, JULY/AUGUST 2014 www.WORLDNEUROSURGERY.org 215
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were sorted systematically for sports
participation by medical professionals.
Data were collected from patients’files
and followed a standardized questionnaire
for biodemographic characteristics, pres-
ence of symptoms compatible with cervical
myelopathy, and registration of radiolog-
ical findings of atlanto-occipital axial
instability. Aside from assessing the prac-
tice of previous physical activities, this
interview screened for the occurrence
of neurological and other sports-limiting
complaints. Symptoms were considered
positive if there were signs of significant
cervical myelopathy, characterized by
motor deficit, sphincter disorder, recent
difficulty climbing stairs, recent balance
impairments during gait, or cervical pain.
Atlanto-occipital instability (AOI) was
defined by a lateral radiographic view en-
compassing the upper cervical spine and
the base of the skull, through the Rules of
12 or Harris measurements. These rules
use the values of the basion-dens interval
(BDI) or the basion-axial interval (BAI)
(Figure 1). Values >12 mm were considered
positive. Moreover, the Wiesel-Rothman
line also was considered for AOI. This line
is traced perpendicularly to the posterior
edge of the clivus and considered positive
if it does not reach the tip of the odontoid.
The target-film distance was 1 m, and the
measurements were made directly on the
radiographs without correction for magni-
fication (Figure 2)(12, 13). Although there
are other assessment measurements for
such instability, we decided to use these
parameters because they were more sensi-
tive and specific when compared with other
measurements, according to the Consensus
Statement of the Spine Trauma Study Group
2007 (5).
Atlantoaxial instability (AAI) was
defined with the same lateral radiographic
view of the skull-spine transition in the
neutral position. The distance between the
anterior border of the odontoid apophysis
of the axis and the posterior border of the
atlas arch was considered widened if it
was larger than 3 mm for adults (Figure 3)
(16, 23).
Qualitative variables were summarized
as percentages, and the description of the
quantitative variables used means and
standard deviations. The association be-
tween qualitative variables was verified
through the
c
2
test. Statistical significance
was set at 5%.
RESULTS
Eighty patients with DS were assessed, 41
(51.2%) of whom were male, and the mean
age was 21.6 3.4 years, ranging from 18
to 41 years. Fourteen patients (17.5%) pre-
sented with AOI, 9 (11.2%) had AAI, and 2
patients (2.5%) presented with both AOI
and AAI. There was no statistically signifi-
cant difference between the groups
regarding age or gender (Table 1).
Symptoms associated with cervical
instability were present in only 3 pa-
tients (3.8%), 2 female and 1 male. One
patient had AOI and another had AAI,
and because the third subject showed
no instability, the investigation went further
and demonstrated an intramedullary neo-
plastic process.
Among the 14 patients who presented
with AOI, 8 were diagnosed only through
the Wiesel-Rothman line criterion, whereas
3 were diagnosed through the Rules of 12
and 3 other cases were diagnosed by pre-
senting both criteria. Thus, a tendency can
be observed for the Wiesel-Rothman line
method to be more sensitive (11 cases) than
the Rules of 12 method (6 cases), however,
this difference was not statistically signifi-
cant, i.e., one cannot affirm that the former
method is more effective to establish AOI
than the Rules of 12 method. Tab l e 2 shows
the agreement between these diagnostic
methods as 86.3%.
DISCUSSION
The prevalence found in the present study
for both AOI (17.5%) and AAI (11.2%) was
similar to that found in other studies, esti-
mated by some authors as being between
10% and 40% (2-4, 19, 22).Somepublished
studies on AOI have used different radio-
logical standards, with a prevalence that
varies from 8.5% to 71%, according to the
criteria (15). The same occurs with AAI,
particularly with the normality threshold
value of the odontoid apophysis distance of
the axis and the posterior border of the
anterior arch of the atlas and whether there
was any correction of the magnification (8).
The diagnosis of AAI in our study used
measurements >3mmforadults,asthere
were no children (23); however, some
studies used parameters for adults that
ranged from 4 to 5 mm (1, 19).Itisimportant
Figure 1. Measurements illustrating the
Rules of 12 or Harris measurements. (based
on Bono et al. [5]).
Figure 2. Normal anatomic relationships of
the skull base and atlas. A line drawn along
the edge of the clivus (C) intersecting the
top of the odontoid process (white line). The
occipital condyle (long white arrows)
occupying the condylar fossa (arrow heads)
of the atlas.
Figure 3. Intervals between the axis and
dens. The atlantodens interval (ADI) and the
posterior atlantodens interval (PADI).
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MARCELO EL-KHOURI ET AL. ATLANTO-OCCIPITAL AND ATLANTOAXIAL INSTABILITY

to consider the inaccuracy and the variation
of measured distance caused by technical
aspects such as positioning, quality of the
film, or obser ver inconsistency (15),whichis
why it is fundamental to carefully follow the
standardized positioning—that is, the
centering of the occipitocervical joint at a
distanceof 1 m with no magnification(5, 1 2).
In the present study, the evaluations were
made with digital radiographic equipment,
which reduces the chance of measurement
errors to practically nil as long as the bone
structures are properly identified. Even so,
the plain radiograph is still one of the best
screening methods to detect AAI (8, 20).
Some authors have suggested the use of
computed tomography or even dynamic
magnetic resonance for the diagnosis,
especially if the patient presents specific
symptoms and cervical radiographs that
show no alterations (6, 9, 15);however,its
reproducibility is low (15).Evenso,we
believe it is necessary to point out that these
last 2 methods must be reserved only for
individuals whose initial scan was incon-
clusive with the simple radiological exami-
nation, which is cheaper and more
innocuous.
In the population with DS, AAI can be
due to osseous deformities, because up to
6% of these individuals have os odontoi-
deum. However, the ligament laxity that is
characteristic of these individuals may
result in a laxness of the transverse liga-
ment, reducing the stability of the dens
with the anterior arch of the first cervical
vertebra (11). Similarly, AOI can be attrib-
uted to an osseous deformity with the in-
congruity of the articular facets of the
occipital condyles and the first cervical
vertebra due to the relative absence of
concavity (7), added to the aforementioned
ligament laxity.
The literature also shows variations
regarding the use of the plain radiographic
view used in the study, with most studies
using the lateral view in flexion, extension,
and neutral positions. The methods of
assessment differ according to the authors’
preferences. All methods, however, have
limitations, and some do not have a
parameter of normality established for chil-
dren (15, 18). According to the Consensus
Statement of the Spine Trauma Study Group
(5), the Rules of 12 technique is the most
useful, sensitive, and reproducible to deter-
mineAOIinDSaswellasinother
conditions.
The correlation between the radiolog-
ical findings and the symptoms was very
low, which is also in agreement with the
literature (1). This is why our group would
like to emphasize the importance of peri-
odic follow-up on these patients, espe-
cially when the patient is allowed to take
part in sports programs, as seen in our
Clinic. The screening recommendation for
cervical instability in these children is that
at least 1 cervical image is collected after
3 years of age, although adherence to this
is not complete (14, 25). Another point to
be raised is that symptoms were highly
correlated with the radiographic findings
and should be exhaustively investigated
when present, although they are rather
rare.
Regarding the age of the studied pa-
tients, although the mean age of the pa-
tients with radiological instability was high
(22 years for AOI and 18.5 years for AAI), it
was not statistically higher than the mean
age of all of the assessed patients, which
indicates no association between such
musculoskeletal alteration and age. Cross-
sectional studies have monitored the fre-
quency and extent of AAI in several children
with DS and have generally observed that it
evolves in the direction of reducing the
number of cases and the degree of the
excursion of 1 bone in relation to the other
at the end of the monitoring periods, which
varied from 5 to 13 years. Despite some
patients evolving toward increased insta-
bility, these studies indicate that this
instability does not tend to progress toward
clinically relevant subluxation, but that
when osseous deformities are identified,
the recommendation is still to monitor the
patients regularly (11). On the other hand,
there are no longitudinal studies on chil-
dren with AOI that support a clinical treat-
ment in spite of the recommendation for
more regular monitoring should there be
any osseous deformity.
Regarding the sports advice in these
cases, one option is a conservative treat-
ment with regular radiological evaluations
and the avoidance of activities that submit
the head and neck to stress, such as con-
tact sports or those with head movements.
Surgical treatment must be recommended
in cases of greater instability and in cases
with more intense symptoms, such as pain
that is resistant to clinical treatment and
signs of progressive neurological decline
(4, 11, 19, 21). The prevalence of degen-
erative signs in the upper cervical column
in individuals with DS correlates positively
with advancing age (2).
Radiological assessment was unable to
securely classify 9 (11.2%) patients. For
these cases, a conservative approach should
be considered, restricting risky physical
Table 1. Age and Sex According to the Type of Instability
Instability OA AA Both Normal Undetermined
N1492509
Age SD (years) 22.0 9.5 20.8 8.0 20.0 5.6 24.9 6.8 26.5 4.5
P*.279 .161
Male (%) 7 (50.0) 5 (55.6) 2 (100.0) 24 (48.0) 6 (66.7)
P
y
.918 .784
AA, atlantoaxial; OA, occipitoatlantal.
*Descriptive level of Kruskal-Wallis test.
yDescriptive level of
c
2
test.
Table 2. Number of Cases with and
without Occipitoatlanto Instability
According to the Rules of 12 and the
Wiesel-Rothman Line
Wiesel-Rothman Line
Yes
No/
Undetermined Total
Rule of 12
Yes 3 3 6
No/
undetermined
866 74
Total 11 69 80
WORLD NEUROSURGERY 82 [1/2]: 215-218, JULY/AUGUST 2014 www.WORLDNEUROSURGERY.org 217
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MARCELO EL-KHOURI ET AL. ATLANTO-OCCIPITAL AND ATLANTOAXIAL INSTABILITY

activities such as those with quick move-
ments or direct trauma to the head, until
complementary assessment and clinical
follow-up were performed, as recom-
mended by some authors and the American
Academy of Pediatrics (1, 19, 26).
One of the limitations of this study lies
in its attempt to define the cervical in-
stabilities in adults with DS. In a city with
16 million inhabitants such as São Paulo,
and in a country with the continental di-
mensions of Brazil, any attempt to define
the population parameters based on the
data from only one clinic is, at the very
least, too optimistic. However, clinics that
offer sports activities to persons with DS
are scarce in the city as well as across the
country, hence these data represent a
significant portion of this population and
can serve as a parameter for future studies.
It must be understood that even in the
international literature, studies on cervical
instability in adults with DS are scarce.
CONCLUSIONS
We could identify as much as one quarter of
our sample with AOIor AAI, which is similar
to figures previously reported in the litera-
ture. No associated factors were identified.
Symptoms were rare and were not associ-
ated with the presence of any particular
aspect of instability. The comparison be-
tween the Rules of 12 technique and the
Wiesel-Rothman line criterion did not show
a superiority of either that might justify any
preference for one over the other; it is pref-
erable to use a combination of both to in-
crease the method’s sensitivity. Owing to the
high prevalence of cervical instability, the
authors recommend that radiographic or
computed tomographic scans be performed
to investigate individuals undertaking or
aiming to undertake risky activities.
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Conflict of interest statement: The authors declare that the
article content was composed in the absence of any
commercial or financial relationships that could be construed
as a potential conflict of interest.
Received 6 July 2012; accepted 8 February 2014;
published online 14 February 2014
Citation: World Neurosurg. (2014) 82, 1/2:215-218.
http://dx.doi.org/10.1016/j.wneu.2014.02.006
Journal homepage: www.WORLDNEUROSURGERY.org
Available online: www.sciencedirect.com
1878-8750/$ - see front matter ª2014 Elsevier Inc.
All rights reserved.
218 www.SCIENCEDIRECT.com WORLD NEUROSURGERY,http://dx.doi.org/10.1016/j.wneu.2014.02.006
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MARCELO EL-KHOURI ET AL. ATLANTO-OCCIPITAL AND ATLANTOAXIAL INSTABILITY